SHKBP1

protein-coding

SH3KBP1 binding protein 1, the group of WD repeat domain containing

Gene summary

Enables identical protein binding activity. Predicted to be involved in positive regulation of epidermal growth factor receptor signaling pathway. Predicted to be located in lysosome and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_138392.4

Inheritance

—

ClinVar variants

U:116B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr19:40,576,853-40,591,399

External References & Databases

Ensembl (ENSG00000160410)

Transcript & Mutation Effects

hg38 • Region Span ~14.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SHKBP1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 104

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138392.4. 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			2 clinvar	1 clinvar		3
missense			108 clinvar	1 clinvar		109
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	116	2	0	118

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138392.4	RefSeq	NP_612401.2	18	MANE Select
ENST00000291842.10	Ensembl	ENSP00000291842.4	18	MANE Select
ENST00000593764.5	Ensembl	ENSP00000471173.1	5	Standard
ENST00000594298.5	Ensembl	ENSP00000471296.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of epidermal growth factor receptor signaling pathway
protein homooligomerization

Molecular Function

protein binding

Cellular Component

lysosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000291842
Coding exons: 18
Length: 14549
Individuals with no LoFs: 125649
Homozygous LoFs: 0
Heterozygous LoFs: 99
Defined: 125748
p: 0.000394

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.98	343	463	0.741	0.0000311	4494
Missense (PolyPhen)		80	121.9	0.65628		1155
Synonymous	0.127	190	192	0.988	0.0000130	1518
Loss of Function	2.91	18	37.2	0.484	0.00000199	378

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.0010	0.00098	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00044	0.00044	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0.00051	0.00049	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits CBL-SH3KBP1 complex mediated down-regulation of EGFR signaling by sequestration of SH3KBP1. Binds to SH3KBP1 and prevents its interaction with CBL and inhibits translocation of SH3KBP1 to EGFR containing vesicles upon EGF stimulation. {ECO:0000250|UniProtKB:Q6P7W2}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.791
RVIS EVS: -1.17
RVIS percentile EVS: 6.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.970

Gene Damage Prediction

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