Table 1 Genes/loci harboring rare variants in AD that need independent replication

AARD

Alanine and arginine rich domain containing protein

8q24.11

Gene burden

[71]

N.A.

ABCA1

ATP binding cassette subfamily A member 1

9q31.1

rs137854495, NM_005502.4:c.2810C>T:p.Ala937Val

[70]

Aβ pathway

Lipoprotein metabolism

ADAM10

ADAM metallopeptidase domain 10

15q21.3

rs61751103, NM_001110.4:c.510G>C:p.Gln170His

rs145518263, NM_001110.4:c.541A>G: p.Arg181Gly

[72]

Aβ pathway

Apoptosis, phagocytosis, autophagy

ADAM17

ADAM metallopeptidase domain 17

2p25.1

rs142946965, NM_003183.6:c.644G>T:p.Arg215Ile

[73]

Aβ pathway

Immune system

Apoptosis, phagocytosis, autophagy

ANXA5

Annexin A5

4q27

Gene burden

[71]

Immune system

APC

APC regulator of WNT signaling pathway

5q22.2

Spatial clustering

[68]

Aβ pathway

Axonal pathfinding

Synaptic plasticity

ASRGL1

Asparaginase and isoaspartyl peptidase 1

11q12.3

chr11:62,343,562:G>C*

[60]

Axonal guidance and cytoskeleton function

Apoptosis, phagocytosis, autophagy

BACE2

Beta-secretase 2

21q22.2-q22.3

12Kb intronic deletion

[74]

Aβ pathway

Apoptosis, phagocytosis, autophagy

C1orf173/ERICH3

Glutamate rich 3

1p31.1

Gene burden

[71]

N.A.

C15ORF41/CDIN1

CDAN1 interacting nuclease 1

15q14

rs141228575, NM_001130010.3:c.213-2446C>T

rs147002962, NM_001130010.3:c.102-13586C>G

[68]

Erythrocyte differentiation

C2CD3

C2 domain containing 3 centriole elongation regulator

11q13.4

Spatial clustering

[68]

Cilium assembly

Ciliary basal body plasma membrane docking

CASP7

Caspase 7

10q25.3

rs116437863, NM_001267057.1:c.1045A>G:p.Arg297Gly

[71]

Aβ pathway

Immune system

Apoptosis, phagocytosis, autophagy

CD2AP

CD2 associated protein

6p12.3

rs116754410, NM_012120.3:c.1898A>G:p.Lys633Arg

rs138727736, NM_012120.3: c.1120A>G:p.Thr374Ala

[54]

Immune system

Cytoskeleton function

BBB integrity

Apoptosis, phagocytosis, autophagy

CD55

CD55 molecule (Cromer blood group)

1q32.2

chr1:207461994C>T (upstream of CD55)

[75]

Immune system

CLDN17

Claudin 17

21q21.3

Homozygosity and gene burden

[76]

BBB integrity

CLSTN2

Calsyntenin 2

3q23

Spatial clustering

[68]

Morphology of synaptic complexes

Calcium-mediated postsynaptic signaling

Episodic memory

Signal transduction

CR1

Complement C3b/C4b receptor 1

1q32.2

rs11587944, NM_000651.6:c.313C>T:p.Arg105Cys

rs372477607, NM_000651.6:c.4021C>T:p.Pro1341Ser

[60]

Aβ pathway

Immune system

Apoptosis, phagocytosis, autophagy

CSF1R

Colony stimulating factor 1 receptor

5q32

rs281860278, NM_001288705.3:c.2603T>G:p.Leu868Arg

rs748641028, NM_001288705.3: c.2073G>C: p.Gln691His

rs111943087, NM_001288705.3:c.2107C>T:p.His703Tyr

[37]

Immune system

BBB integrity

Cytoskeleton function

CTNNA2

Catenin alpha 2

2p12

Spatial clustering

[68]

Neuronal migration and neuritic outgrowth

Cell-cell adhesion

CTSF

Cathepsin F

11q13.2

rs200426008, NM_003793.4:c.1243G>A: p.Gly415Arg

[66]

Immune system

Apoptosis, phagocytosis, autophagy

DPP6

Dipeptidyl peptidase like 6

7q36.2

Chr7:149,704,610 - 153,786,893 paracentric inversion*

[77]

Synaptic plasticity

EPHA1

EPH receptor A1

7q34-q35

rs202178565, NM_005232.5:c.1379C>T:p.Pro460Leu

[54]

Immune system

Axonal guidance

Synaptic plasticity

BBB integrity

Apoptosis, phagocytosis, autophagy

ERN1

Endoplasmic reticulum to nucleus signaling 1

17q23.3

rs56201815, NM_001433.5:c.1017C>T:p.Asp339=

[69]

Autophagy

Unfolded protein response (UPR) and neuronal apoptosis

EXOC3L4/C14orf73

Exocyst complex component 3 like 4

14q32.32

rs117708804, NM_001077594.1:c.1126G>T:p.Ala376Ser

rs10142287, NM_001077594.1:c.687C>A:p.Pro229=

rs9324055, NM_001077594.1: c.889G>A: p.Val297Met

rs148718670, NM_001077594.1: c.1937G>A: p.Arg646Gln

[78]

N.A.

FERMT2

FERM domain containing kindlin 2

14q22.1

rs17125944, NM_001134999.1:c.158-14555A>G

[70]

Cell adhesion

FNBP1L

Formin binding protein 1 like

1p22.1

rs192471919, NM_001164473.2:c.1652-634T>C

[68]

Endocytosis

Autophagy

Neurite elongation and axonal branching (neuroplasticity)

FSIP2

Fibrous sheath interacting protein 2

2q32.1

rs531170562, NM_173651.4:c.742C>T:p.Arg248Cys

rs552474258, NM_173651.4:c.743G>T:p.Arg248Leu

[70]

Spermatogenesis

IGHG3

Immunoglobulin heavy constant gamma 3 (G3m marker)

14q32.33

rs77307099, ENST00000390551.2:c.938G>A, p.Ser313Asn

rs78376194, ENST00000390551.2: c.939C>T, p.Ser313=

rs12890621, ENST00000390551.2: c.674A>T, p.Tyr225Phe

[79]

Neuroinflammation

KIF2A

Kinesin family member 2A

5q12.1

Spatial clustering

[68]

Mitotic spindle activity and normal brain development Microtubule-based processes

Ciliogenesis

Cortical development

Spinal cord injuries

LHX9

LIM homeobox 9

1q31.3

Spatial clustering

[68]

Development of the forebrain

LincRNA LINC00298

Long intergenic noncoding RNA LINC00298

2p25.1

rs147918541, chr2:8073233:G>A

[68]

May be involved in neuronal plasticity

LncRNA AC099552.4

Long non-coding RNA AC099552.4

7q36.3

chr7:154988675:G>A

[79]

Gene expression regulation

LncRNA RP11-433J8

Long non-coding RNA RP11-433J8

14q32.2

chr14:97228875:A>G

[70]

N.A.

MAPT

Microtubule associated protein tau

17q21.31

NM_001123066.3:c.370C>A: p.Gln124Ly

NM_001123066.3:c.2203T>G:p.Ser735Ala

[80]

Tau pathway

Axonal guidance and cytoskeleton functioning

Apoptosis, phagocytosis, autophagy

MARK4

Microtubule affinity regulating kinase 4

19q13.32

NM_001199867.1: c.946_951delGGTGAGinsGAT:p.Gly316_Glu317delinsAsp

[74]

Tau pathway

Cytoskeleton function

Apoptosis, phagocytosis, autophagy

MYRF

Myelin regulatory factor

11q12.2

rs34038946, NM_001127392.3:c.2167G>A:p.Ala723Thr

[60]

Lipid metabolism

Synaptic plasticity

NALCN

Sodium leak channel, non-selective

13q32.3-q33.1

Spatial clustering

[68]

Neuronal excitability

PIN1

Peptidylprolyl cis/trans isomerase, NIMA-interacting 1

19p13.2

c.477C>T, p.Thr152Met*

[81]

Aβ pathway

Tau pathway

Apoptosis, phagocytosis, autophagy

PINX1

PIN2 (TERF1) interacting telomerase inhibitor 1

8p23.1

Gene burden

[82]

Telomere integrity

PRKCH

Protein kinase C eta

14q23.1

Spatial clustering

[68]

Signal transduction

PSD2

Pleckstrin and Sec7 domain containing 2

5q31.2

rs138380367, NM_032289.4:c.1549G>A: p.Gly517Ser

[83]

Endolysosomal transport

RTN3

Reticulon 3

11q13.1

rs372883387, NM_001265589.2:c.-8G>T

NM_001265589.2:c.42C>T: p.Ser14=

NM_001265589.2: c.116C>T:p.Thr39Met

rs11551944: NM_001265589.2:c.17C>A:p.Ala6Glu

[84]

Aβ pathway

Lipid metabolism

Apoptosis, phagocytosis, autophagy

RUFY1

RUN and FYVE domain containing 1

5q35.3

rs138313632,NM_025158.5:c.2113T>G: p.Ser705Ala

[83]

Endolysosomal transport

SEL1L

SEL1L adaptor subunit of ERAD E3 ubiquitin ligase

14q31.1

rs74065194, chr14:82182068: C>T

[68]

Aβ pathway

Endoplasmic reticulum-associated degradation (ERAD)

ER stress and cell death

SEZ6

Seizure related 6 homolog

17q11.2

rs371753097, NM_178860.5:c.1844G>A:p.Arg615His

[85]

Aβ pathway

Synaptic plasticity

SLC24A4-RIN3

Solute carrier family 24 member 4-Ras and Rab interactor 3

14q32.12

SLC24A4:rs10498633, NM_153646.4:c.1255+4000G>T

RIN3:rs147042536, NM_024832.5:c.2377T>C, :p.Tyr793His

RIN3: rs150221413, NM_024832.5:c.189G>T, :p.Trp63Cys

[60, 83]

SLC24A4: Na+Ca2+, K+ exchange

RIN3:Endolysosomal transport

SRCAP

Snf2 related CREBBP activator protein

16p11.2

10 ultra-rare missense mutations

[86]

Gene expression regulation

SYTL3

Synaptotagmin like 3

6q25.3

Spatial clustering

[68]

Vesicle trafficking

TCIRG1

T cell immune regulator 1, ATPase H+ transporting V0 subunit a3

11q13.2

rs34227834, NM_006019.4:c.482C>T, : p.Pro161Leu

[83]

Endolysosomal transport

Immune system

TTC3

Tetratricopeptide repeat domain 3

21q22.13

rs377155188, NM_001001894.2:c.3113C>G: p.Ser1038Cys

[87]

Aβ pathway

TYROBP

Transmembrane immune signaling adaptor TYROBP

19q13.12

rs200649978, NM_003332.4:c.5G>A:p.Gly2Glu

NM_003332.3:c.163G>T: p.Val55Leu

[88]

Aβ pathway

Immune system

Lipid metabolism

Apoptosis, phagocytosis, autophagy

VPS35

VPS35 retromer complex component

16q11.2

NM_018206.6:c.1874T>C: p.Leu625Pro

[74]

Aβ pathway

Apoptosis, phagocytosis, autophagy

VWA2

Von Willebrand factor A domain containing 2

10q25.3

rs79009215, NM_001272046.2:c.1096G>A:p.Val366Met

[89]

N.A.

ZNF655

Zinc finger protein 655

7q22.1

Gene burden

[79]

Gene expression regulation