STAMBP

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

Basic information

Region (hg38): 2:73828916-73873659

Links

ENSG00000124356 ∙ NCBI:10617 ∙ OMIM:606247 ∙ HGNC:16950 ∙ Uniprot:O95630 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly-capillary malformation syndrome (Definitive), mode of inheritance: AR
• microcephaly-capillary malformation syndrome (Strong), mode of inheritance: AR
• microcephaly-capillary malformation syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly-capillary malformation syndrome	AR	General	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	Dermatologic; Neurologic	23542699

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STAMBP gene.

• not provided (7 variants)
• Microcephaly-capillary malformation syndrome (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STAMBP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	26	3	31
missense	2	4	73	3		82
nonsense	3	3				6
start loss						0
frameshift	6					6
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2				2
splice region		3	4	6	1	14
non coding				27	18	45
Total	11	9	76	56	21

Highest pathogenic variant AF is 0.0000329

Variants in STAMBP

This is a list of pathogenic ClinVar variants found in the STAMBP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-73830569-C-T			Likely benign (Mar 03, 2019)
2-73830859-G-GTC		Microcephaly-capillary malformation syndrome	Pathogenic (Oct 03, 2023)
2-73830868-T-A			Uncertain significance (Aug 23, 2022)
2-73830868-T-C		not specified • Microcephaly-capillary malformation syndrome	Benign (Feb 01, 2024)
2-73830870-G-A			Uncertain significance (Dec 02, 2021)
2-73830885-C-T			Uncertain significance (Oct 24, 2022)
2-73830888-C-T			Uncertain significance (Feb 16, 2023)
2-73830889-C-T		Microcephaly-capillary malformation syndrome • STAMBP-related disorder	Likely benign (Jan 18, 2024)
2-73830890-G-A			Uncertain significance (Jul 19, 2022)
2-73830897-G-A			Uncertain significance (Dec 03, 2021)
2-73830905-G-C			Uncertain significance (Jun 05, 2022)
2-73830915-A-G			Uncertain significance (Aug 17, 2023)
2-73830923-A-G			Uncertain significance (Dec 29, 2021)
2-73830927-C-T		Inborn genetic diseases	Uncertain significance (Dec 07, 2023)
2-73830928-G-A		STAMBP-related disorder	Likely benign (Jul 03, 2022)
2-73830939-A-G			Uncertain significance (Nov 08, 2022)
2-73830943-A-C			Uncertain significance (Dec 03, 2021)
2-73830956-C-T			Uncertain significance (Jul 19, 2022)
2-73830960-G-A		Inborn genetic diseases	Uncertain significance (May 23, 2024)
2-73830962-TAC-AA			Pathogenic (Mar 14, 2016)
2-73830968-C-G		Microcephaly-capillary malformation syndrome	Uncertain significance (Jun 07, 2022)
2-73830968-C-T		Microcephaly-capillary malformation syndrome	Pathogenic/Likely pathogenic (Jun 26, 2023)
2-73830969-G-A		Microcephaly-capillary malformation syndrome	Uncertain significance (Apr 04, 2024)
2-73830981-A-G		Microcephaly-capillary malformation syndrome	Likely pathogenic (Jun 15, 2023)
2-73831027-A-G			Likely benign (Oct 22, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STAMBP	protein_coding	protein_coding	ENST00000394070	9	44701

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000545	0.994	125717	0	30	125747	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.886	202	241	0.839	0.0000131	2774
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000516	0.000514
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.000109	0.000109
South Asian	0.000133	0.000131
Other	0.00	0.00

dbNSFP

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.
• Pathway: Endocytosis - Homo sapiens (human);EGF-EGFR Signaling Pathway;Post-translational protein modification;Metabolism of proteins;Metalloprotease DUBs;EGFR1;Deubiquitination;Internalization of ErbB1 (Consensus)

Recessive Scores

• pRec: 0.129

Intolerance Scores

• loftool: 0.837
• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.15

Haploinsufficiency Scores

• pHI: 0.199
• hipred: Y
• hipred_score: 0.756
• ghis: 0.578

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.850

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Stambp
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype

Gene ontology

• Biological process: mitotic cytokinesis;JAK-STAT cascade;positive regulation of cell population proliferation;negative regulation of phosphatidylinositol 3-kinase signaling;protein deubiquitination;negative regulation of neuron apoptotic process;negative regulation of Ras protein signal transduction;protein K63-linked deubiquitination
• Cellular component: nucleus;nucleoplasm;endosome;early endosome;cytosol;plasma membrane;membrane;cleavage furrow;extracellular exosome
• Molecular function: thiol-dependent ubiquitin-specific protease activity;protein binding;metallopeptidase activity;protein domain specific binding;metal ion binding;Lys63-specific deubiquitinase activity