SORBS1

protein-coding

sorbin and SH3 domain containing 1

Gene summary

This gene encodes a CBL-associated protein which functions in the signaling and stimulation of insulin. Mutations in this gene may be associated with human disorders of insulin resistance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

Previous symbols:

SH3D5

MANE transcript

NM_001034954.3

Inheritance

—

ClinVar variants

U:205B:20

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr10:95,311,771-95,561,414

External References & Databases

Ensembl (ENSG00000095637)

Transcript & Mutation Effects

hg38 • Region Span ~249.6 kb

Loading mutation effect viewer...

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 SORBS1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 203

not providedTotal: 10

Prostate cancerTotal: 1

SORBS1-associated Hirschsprung diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001034954.3. 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			1 clinvar	2 clinvar	4 clinvar	7
missense			197 clinvar	12 clinvar	2 clinvar	211
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	205	14	6	225

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 514 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001034954.3	RefSeq	NP_001030126.2	31	MANE Select
ENST00000371247.7	Ensembl	ENSP00000360293.2	31	MANE Select
NM_001034955.2	RefSeq	NP_001030127.2	31	Standard
NM_001034956.2	RefSeq	NP_001030128.2	28	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Adherens junction - Homo sapiens (human)
PPAR signaling pathway - Homo sapiens (human)
Insulin signaling pathway - Homo sapiens (human)
Integrin-mediated Cell Adhesion
PPAR signaling pathway

Biological Process

muscle contraction
cell-matrix adhesion
insulin receptor signaling pathway
cellular response to insulin stimulus
stress fiber assembly

Molecular Function

actin binding
SH3/SH2 adaptor activity
insulin receptor binding
protein binding
cytoskeletal protein binding

Cellular Component

stress fiber
nucleus
centrosome
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371247
Coding exons: 31
Length: 249644
Individuals with no LoFs: 125688
Homozygous LoFs: 0
Heterozygous LoFs: 60
Defined: 125748
p: 0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.50	625	740	0.845	0.0000425	8353
Missense (PolyPhen)		211	280.7	0.7517		3200
Synonymous	1.22	261	287	0.909	0.0000177	2606
Loss of Function	4.44	33	74.3	0.444	0.00000408	842

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00025	0.00024	rare
South Asian	0.00020	0.00020	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor. Required for insulin- stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesions (By similarity). {ECO:0000250|UniProtKB:Q62417}.;

Recessive Scores

pRec: 0.162

Intolerance Scores

LoFtool: 0.809
RVIS EVS: 0.48
RVIS percentile EVS: 79.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.511

Gene Damage Prediction

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