SH3D19

protein-coding

SH3 domain containing 19

Gene summary

This gene encodes a multiple SH3 domain-containing protein, which interacts with other proteins, such as EBP and members of ADAM family, via the SH3 domains. This protein may be involved in suppression of Ras-induced cellular transformation and Ras-mediated activation of ELK1 by EBP, and regulation of ADAM proteins in the signaling of EGFR-ligand shedding. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

MANE transcript

NM_001378122.1

Inheritance

—

ClinVar variants

U:121B:13

Top phenotype

SH3D19-related disorder

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr4:151,102,751-151,409,365

External References & Databases

Ensembl (ENSG00000109686)

Transcript & Mutation Effects

hg38 • Region Span ~306.6 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 SH3D19 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 174

SH3D19-related disorderTotal: 9

not providedTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Essential tremorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001378122.1. 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			2 clinvar	3 clinvar		5
missense			114 clinvar	8 clinvar	2 clinvar	124
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	121	11	2	134

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 79 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001378122.1	RefSeq	NP_001365051.1	20	MANE Select
ENST00000604030.7	Ensembl	ENSP00000488951.1	20	MANE Select
NM_001009555.4	RefSeq	NP_001009555.3	15	Standard
NM_001128923.2	RefSeq	NP_001122395.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Golgi Associated Vesicle Biogenesis
Clathrin derived vesicle budding
trans-Golgi Network Vesicle Budding
Vesicle-mediated transport
Membrane Trafficking

Biological Process

cytoskeleton organization
regulation of cell morphogenesis
positive regulation of membrane protein ectodomain proteolysis

Molecular Function

protein binding

Cellular Component

nucleoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304527
Coding exons: 15
Length: 222882
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125747
p: 0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.583	385	419	0.920	0.0000207	5111
Missense (PolyPhen)		119	125.51	0.94811		1588
Synonymous	1.02	132	148	0.893	0.00000733	1601
Loss of Function	3.49	16	39.7	0.403	0.00000242	460

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00082	0.00081	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00023	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in regulating A disintegrin and metalloproteases (ADAMs) in the signaling of EGFR-ligand shedding. May be involved in suppression of Ras-induced cellular transformation and Ras-mediated activation of ELK1. Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:14551139, ECO:0000269|PubMed:15280379, ECO:0000269|PubMed:21834987}.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.732
RVIS EVS: -0.09
RVIS percentile EVS: 47.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.599

Gene Damage Prediction

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