SDK1

protein-coding

sidekick cell adhesion molecule 1, the group of Fibronectin type III domain containing|I-set domain containing|Ig-like cell adhesion molecule family

Gene summary

The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains six immunoglobulin-like 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

MANE transcript

NM_152744.4

Inheritance

—

ClinVar variants

U:512B:54

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr7:3,301,252-4,269,000

External References & Databases

Ensembl (ENSG00000146555)

Transcript & Mutation Effects

hg38 • Region Span ~967.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SDK1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 499

not providedTotal: 37

Prostate cancerTotal: 1

Autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152744.4. 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			10 clinvar	16 clinvar	9 clinvar	35
missense			487 clinvar	23 clinvar	6 clinvar	516
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	0	512	39	15	566

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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_152744.4	RefSeq	NP_689957.3	45	MANE Select
ENST00000404826.7	Ensembl	ENSP00000385899.2	45	MANE Select
NM_001079653.2	RefSeq	NP_001073121.1	17	Standard
ENST00000389531.7	Ensembl	ENSP00000374182.3	44	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
behavioral response to cocaine

Molecular Function

identical protein binding

Cellular Component

plasma membrane
integral component of membrane
cell junction
synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000404826
Coding exons: 45
Length: 967553
Individuals with no LoFs: 125679
Homozygous LoFs: 0
Heterozygous LoFs: 69
Defined: 125748
p: 0.000274

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.10	1558	1.34e+3	1.16	0.0000896	14119
Missense (PolyPhen)		368	388.16	0.94806		3911
Synonymous	-6.61	803	597	1.34	0.0000471	4621
Loss of Function	6.70	31	105	0.295	0.00000499	1208

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00099	0.00072	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.000050	0.000046	rare
European (Non-Finnish)	0.00023	0.00020	rare
South Asian	0.00020	0.00020	rare
Other	0.00051	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adhesion molecule that promotes lamina-specific synaptic connections in the retina. Expressed in specific subsets of interneurons and retinal ganglion cells (RGCs) and promotes synaptic connectivity via homophilic interactions. {ECO:0000250|UniProtKB:Q8AV58}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.433
RVIS EVS: -4.63
RVIS percentile EVS: 0.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.236

Gene Damage Prediction

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