STAMBP

Chr 2AR

STAM binding protein

Also known as: AMSH, MICCAP

NCBI Gene: 10617 ENSG00000124356 OMIM: 606247

STAMBP encodes a zinc metalloprotease that cleaves specific polyubiquitin chains and regulates endosomal sorting of cell surface receptors to lysosomes, playing key roles in cytokine signaling, BMP signaling, and receptor-mediated endocytosis. Autosomal recessive mutations cause microcephaly-capillary malformation syndrome, affecting brain development and vascular formation. The gene shows low constraint to loss-of-function variation (pLI 0.00005), consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.761 OMIM phenotype

Clinical Summary— STAMBP

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

29 unique Pathogenic / Likely Pathogenic· 104 VUS of 253 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — STAMBP

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.000

Z-score 2.43

OE 0.46 (0.29–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.89Z-score

OE missense 0.84 (0.75–0.94)

202 obs / 240.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.29–0.76)

0≤0.351.4

Missense OE?0.84 (0.75–0.94)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 11 / 23.8Missense obs/exp: 202 / 240.7Syn Z: -0.03

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSTAMBP-related microcephaly-capillary malformation syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6745th %ile

GOF

0.5758th %ile

LOF

0.2968th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

253 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13

Likely Pathogenic16

VUS104

Likely Benign70

Benign24

Conflicting7

Pathogenic

Likely Pathogenic

104

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	3	2	0	13
Likely Pathogenic	9	4	3	0	16
VUS	0	97	4	3	104
Likely Benign	0	3	33	34	70
Benign	0	0	21	3	24
Conflicting	—				7
Total	17	107	63	40	234

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

10 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap STAMBP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →