STAMBP

protein-coding

STAM binding protein, the group of JAMM/MPN+ metallopeptidase family

Gene summary

Cytokine-mediated signal transduction in the JAK-STAT cascade requires the involvement of adaptor molecules. One such signal-transducing adaptor molecule contains an SH3 domain that is required for induction of MYC and cell growth. The protein encoded by this gene binds to the SH3 domain of the signal-transducing adaptor molecule, and plays a critical role in cytokine-mediated signaling for MYC induction and cell cycle progression. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_213622.4

Inheritance

ClinVar variants

P:26U:102B:49

Top phenotype

Microcephaly-capillary malformation syndrome

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr2:73,828,916-73,873,659

External References & Databases

Ensembl (ENSG00000124356)

Transcript & Mutation Effects

hg38 • Region Span ~44.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephaly-capillary malformation syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013659

Submitter: G2P

microcephaly-capillary malformation syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013659

Submitter: PanelApp Australia

microcephaly-capillary malformation syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013659

Submitter: Orphanet

microcephaly-capillary malformation syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013659

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Microcephaly-capillary malformation syndromeAR

Manifestation: Dermatologic; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 23542699

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STAMBP variants in ClinVar

5 Conditions Cataloged

not providedTotal: 158

Inborn genetic diseasesTotal: 60

Microcephaly-capillary malformation syndromeTotal: 34

not specifiedTotal: 23

STAMBP-related disorderTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_213622.4. 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			5 clinvar	40 clinvar		45
missense	2 clinvar	7 clinvar	95 clinvar	9 clinvar		113
nonsense	1 clinvar	6 clinvar				7
start loss						0
frameshift	7 clinvar					7
splice donor/acceptor (+/-2bp)		3 clinvar	2 clinvar			5
Total	10	16	102	49	0	177

Highest pathogenic variant AF is 0.00011276039

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 119 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_213622.4	RefSeq	NP_998787.1	9	MANE Select
ENST00000394070.7	Ensembl	ENSP00000377633.2	9	MANE Select
NM_001353967.2	RefSeq	NP_001340896.1	9	Standard
NM_001353968.2	RefSeq	NP_001340897.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
EGF-EGFR Signaling Pathway
Post-translational protein modification
Metabolism of proteins
Metalloprotease DUBs

Biological Process

mitotic cytokinesis
JAK-STAT cascade
positive regulation of cell population proliferation
negative regulation of phosphatidylinositol 3-kinase signaling
protein deubiquitination

Molecular Function

thiol-dependent ubiquitin-specific protease activity
protein binding
metallopeptidase activity
protein domain specific binding
metal ion binding

Cellular Component

nucleus
nucleoplasm
endosome
early endosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394070
Coding exons: 9
Length: 44701
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125747
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.886	202	241	0.839	0.0000131	2774
Missense (PolyPhen)		62	92.642	0.66924		1034
Synonymous	-0.0341	91	90.6	1.00	0.00000484	824
Loss of Function	2.43	11	23.8	0.462	0.00000144	263

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Zinc metalloprotease that specifically cleaves 'Lys-63'- linked polyubiquitin chains. Does not cleave 'Lys-48'-linked polyubiquitin chains (By similarity). Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF. Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7. Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes. Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization (By similarity). Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways. {ECO:0000250, ECO:0000269|PubMed:10383417, ECO:0000269|PubMed:11483516, ECO:0000269|PubMed:15314065, ECO:0000269|PubMed:17261583, ECO:0000269|PubMed:23542699}.;
Disease: DISEASE: Microcephaly-capillary malformation syndrome (MICCAP) [MIM:614261]: A congenital disorder characterized by severe progressive microcephaly, early-onset refractory epilepsy, profound developmental delay, and multiple small capillary malformations spread diffusely on the body. Additional more variable features include dysmorphic facial features, distal limb abnormalities, and mild heart defects. {ECO:0000269|PubMed:23542699}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.129

Intolerance Scores

LoFtool: 0.837
RVIS EVS: 0.04
RVIS percentile EVS: 57.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.850

Gene Damage Prediction

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