PMEPA1

prostate transmembrane protein, androgen induced 1

Basic information

Region (hg38): 20:57648392-57711536

Previous symbols: [ "TMEPAI" ]

Links

ENSG00000124225 ∙ NCBI:56937 ∙ OMIM:606564 ∙ HGNC:14107 ∙ Uniprot:Q969W9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PMEPA1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PMEPA1 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						0
missense			12	1		13
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	0	0	13	1	0

Variants in PMEPA1

This is a list of pathogenic ClinVar variants found in the PMEPA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-57652090-C-T		not specified	Uncertain significance (Aug 20, 2023)
20-57652129-T-G		not specified	Likely benign (Sep 17, 2021)
20-57652176-C-A		not specified	Uncertain significance (May 31, 2023)
20-57652211-T-C		not specified	Uncertain significance (Apr 19, 2023)
20-57652292-T-TG		Hereditary disorder of connective tissue	Uncertain significance (Jan 07, 2025)
20-57652295-G-A		not specified	Uncertain significance (Nov 09, 2024)
20-57652369-A-C		not specified	Uncertain significance (Nov 17, 2022)
20-57652418-G-A		not specified	Uncertain significance (Jun 28, 2022)
20-57652484-C-T		not specified	Uncertain significance (Sep 27, 2021)
20-57652532-G-A		not specified	Uncertain significance (Sep 12, 2023)
20-57652537-C-G		not specified	Uncertain significance (Feb 05, 2024)
20-57653079-C-T		not specified	Uncertain significance (May 28, 2024)
20-57659545-A-C		not specified	Uncertain significance (Sep 29, 2023)
20-57659590-T-C		not specified	Uncertain significance (Dec 31, 2024)
20-57659669-G-C		not specified	Uncertain significance (Jul 30, 2024)
20-57709530-G-C		not specified	Uncertain significance (Sep 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PMEPA1	protein_coding	protein_coding	ENST00000341744	4	63145

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.936	0.0640	111940	0	1	111941	0.00000447

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.21	128	173	0.742	0.0000114	1823
Missense in Polyphen		74	91.014	0.81306		804
Synonymous	-0.996	91	79.7	1.14	0.00000592	570
Loss of Function	2.74	0	8.72	0.00	3.73e-7	105

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000593	0.0000593
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000593	0.0000593
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA recruits the intracellular signal transducer and transcriptional modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by the receptor, SMAD2 and SMAD3 then form a heteromeric complex with SMAD4 that translocates to the nucleus to regulate transcription. Through interaction with SMAD2 and SMAD3, LDLRAD4 may compete with ZFYVE9 and SMAD4 and prevent propagation of the intracellular signal (PubMed:20129061, PubMed:24627487). Also involved in down-regulation of the androgen receptor (AR), enhancing ubiquitination and proteasome-mediated degradation of AR, probably by recruiting NEDD4 (PubMed:18703514). {ECO:0000269|PubMed:18703514, ECO:0000269|PubMed:20129061, ECO:0000269|PubMed:24627487}.
• Pathway: Signal Transduction;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Downregulation of TGF-beta receptor signaling;TGF-beta receptor signaling activates SMADs (Consensus)

Recessive Scores

• pRec: 0.167

Intolerance Scores

• loftool: 0.401
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.76

Haploinsufficiency Scores

• pHI: 0.223
• hipred: Y
• hipred_score: 0.629
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.741

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pmepa1

Gene ontology

• Biological process: negative regulation of SMAD protein complex assembly;negative regulation of transforming growth factor beta receptor signaling pathway;androgen receptor signaling pathway;negative regulation of pathway-restricted SMAD protein phosphorylation
• Cellular component: Golgi membrane;plasma membrane;endosome membrane;integral component of membrane;early endosome membrane;intracellular membrane-bounded organelle
• Molecular function: protein binding;WW domain binding;R-SMAD binding