SDK2

protein-coding

sidekick cell adhesion molecule 2, the group of Fibronectin type III domain containing|I-set domain containing

Gene summary

The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains two immunoglobulin domains and thirteen fibronectin type III domains. Fibronectin type III domains are present in both extracellular and intracellular proteins and tandem repeats are known to contain binding sites for DNA, heparin and the cell surface. This protein, and a homologous mouse sequence, are very similar to the Drosophila sidekick gene product but the specific function of this superfamily member is not yet known. Evidence for alternative splicing at this gene locus has been observed but the full-length nature of additional variants has not yet been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001144952.2

Inheritance

ClinVar variants

U:410B:49

Top phenotype

SDK2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr17:73,334,384-73,644,445

External References & Databases

Ensembl (ENSG00000069188)

Transcript & Mutation Effects

hg38 • Region Span ~310.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disabilityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SDK2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 402

SDK2-related disorderTotal: 48

not providedTotal: 17

See casesTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001144952.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				24 clinvar	12 clinvar	36
missense			404 clinvar	9 clinvar	4 clinvar	417
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	410	33	16	459

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001144952.2	RefSeq	NP_001138424.1	45	MANE Select
ENST00000392650.8	Ensembl	ENSP00000376421.3	45	MANE Select
ENST00000424778.1	Ensembl	ENSP00000407098.1	27	Standard
ENST00001112757.1	Ensembl	ENSP00000782562.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

SDK interactions
Cell-cell junction organization
Cell junction organization
Cell-Cell communication

Biological Process

homophilic cell adhesion via plasma membrane adhesion molecules
synapse assembly
retina layer formation
cell-cell junction organization
camera-type eye photoreceptor cell differentiation

Cellular Component

plasma membrane
integral component of membrane
cell junction
synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392650
Coding exons: 45
Length: 309706
Individuals with no LoFs: 125605
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125643
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.68	1055	1.33e+3	0.793	0.0000893	13858
Missense (PolyPhen)		449	604.05	0.74331		6215
Synonymous	-0.526	588	572	1.03	0.0000423	4413
Loss of Function	7.11	27	106	0.255	0.00000534	1165

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00021	0.00020	rare
South Asian	0.000072	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adhesion molecule that promotes lamina-specific synaptic connections in the retina and is specifically required for the formation of neuronal circuits that detect motion. Acts by promoting formation of synapses between two specific retinal cell types: the retinal ganglion cells W3B-RGCs and the excitatory amacrine cells VG3-ACs. Formation of synapses between these two cells plays a key role in detection of motion. Promotes synaptic connectivity via homophilic interactions. {ECO:0000250|UniProtKB:Q6V4S5}.;

Recessive Scores

pRec: 0.121

Intolerance Scores

RVIS EVS: -2.47
RVIS percentile EVS: 0.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.264

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium