TMEM63A

transmembrane protein 63A

Basic information

Region (hg38): 1:225845536-225882380

Previous symbols: [ "KIAA0792" ]

Links

ENSG00000196187 ∙ NCBI:9725 ∙ OMIM:618685 ∙ HGNC:29118 ∙ Uniprot:O94886 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• leukodystrophy, hypomyelinating, 19, transient infantile (Strong), mode of inheritance: AD
• leukodystrophy, hypomyelinating, 19, transient infantile (Limited), mode of inheritance: AD
• leukodystrophy, hypomyelinating, 19, transient infantile (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating, 19, transient infantile	AD	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	Neurologic	31587869; 35718349

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM63A gene.

• Inborn_genetic_diseases (103 variants)
• not_provided (23 variants)
• Leukodystrophy,_hypomyelinating,_19,_transient_infantile (23 variants)
• TMEM63A-related_disorder (10 variants)
• not_specified (7 variants)
• Leukodystrophy (3 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM63A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014698.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				11	1	12
missense	3	5	87	29	4	128
nonsense			1			1
start loss			1			1
frameshift		1	4	1		6
splice donor/acceptor (+/-2bp)			2			2
Total	3	6	95	41	5

Highest pathogenic variant AF is 0.00000684285

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM63A	protein_coding	protein_coding	ENST00000366835	22	36833

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.39e-12	0.982	125532	0	216	125748	0.000859

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.24	384	459	0.837	0.0000261	5273
Missense in Polyphen		142	173	0.8208		2052
Synonymous	0.633	179	190	0.942	0.0000114	1566
Loss of Function	2.43	26	43.2	0.601	0.00000184	519

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00277	0.00277
Ashkenazi Jewish	0.00	0.00
East Asian	0.000980	0.000979
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000795	0.000791
Middle Eastern	0.000980	0.000979
South Asian	0.00153	0.00141
Other	0.00100	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as an osmosensitive calcium-permeable cation channel. {ECO:0000250}.
• Pathway: Neutrophil degranulation;Innate Immune System;Immune System (Consensus)

Intolerance Scores

• loftool: 0.954
• rvis_EVS: 0.58
• rvis_percentile_EVS: 82.34

Haploinsufficiency Scores

• pHI: 0.0730
• hipred: N
• hipred_score: 0.492
• ghis: 0.423

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.347

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem63a
• Phenotype: limbs/digits/tail phenotype; skeleton phenotype

Gene ontology

• Biological process: ion transmembrane transport;neutrophil degranulation
• Cellular component: lysosomal membrane;microtubule organizing center;plasma membrane;integral component of membrane;specific granule membrane;intracellular membrane-bounded organelle;extracellular exosome;tertiary granule membrane
• Molecular function: nucleic acid binding;calcium activated cation channel activity