TMEM53

transmembrane protein 53

Basic information

Region (hg38): 1:44635238-44674481

Links

ENSG00000126106 ∙ NCBI:79639 ∙ OMIM:619722 ∙ HGNC:26186 ∙ Uniprot:Q6P2H8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• craniotubular dysplasia, Ikegawa type (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Craniotubular dysplasia, Ikegawa type	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	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic	33824347

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM53 gene.

• Craniotubular dysplasia, Ikegawa type (2 variants)
• TMEM53-related craniotubular dysplasia (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM53 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			20	1		21
nonsense						0
start loss						0
frameshift	1					1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region	1					1
non coding						0
Total	1	0	21	1	0

Variants in TMEM53

This is a list of pathogenic ClinVar variants found in the TMEM53 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-44635547-C-T		not specified	Uncertain significance (Apr 22, 2024)
1-44636047-G-A		not specified	Uncertain significance (Jul 11, 2023)
1-44636069-A-G		not specified	Uncertain significance (Dec 19, 2022)
1-44636091-G-A		not specified	Uncertain significance (Feb 16, 2023)
1-44636105-G-A		not specified	Uncertain significance (Feb 12, 2024)
1-44636124-G-A		Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy	Pathogenic (Apr 06, 2023)
1-44636130-G-A		Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy	Pathogenic (Mar 29, 2024)
1-44636160-G-A		not specified	Uncertain significance (Dec 03, 2021)
1-44644710-T-C		not specified	Uncertain significance (Nov 17, 2023)
1-44644728-A-G		not specified	Uncertain significance (Aug 10, 2021)
1-44645022-C-T			Likely benign (Jan 01, 2023)
1-44645054-G-C		not specified	Uncertain significance (Mar 26, 2024)
1-44645070-C-T			Likely benign (Jan 01, 2023)
1-44645238-C-T		not specified	Uncertain significance (Dec 28, 2022)
1-44649671-G-T		not specified	Uncertain significance (Dec 21, 2023)
1-44649684-C-A		not specified	Uncertain significance (Jun 09, 2022)
1-44649688-G-A			Likely benign (Sep 01, 2023)
1-44649887-C-T		not specified	Uncertain significance (Dec 11, 2023)
1-44654579-G-A		not specified	Uncertain significance (Oct 29, 2021)
1-44654602-G-A		not specified	Uncertain significance (May 23, 2023)
1-44654665-C-T		not specified	Uncertain significance (Dec 13, 2021)
1-44654677-C-CGGCGTGCCA		Craniotubular dysplasia, Ikegawa type	Uncertain significance (Jul 10, 2023)
1-44654681-G-A		not specified	Uncertain significance (Sep 16, 2021)
1-44654705-G-A		not specified	Uncertain significance (Dec 21, 2023)
1-44654756-G-A		not specified	Uncertain significance (Jun 10, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM53	protein_coding	protein_coding	ENST00000372237	3	39318

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0214	0.914	125736	0	10	125746	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.01	149	188	0.793	0.0000131	1766
Missense in Polyphen		47	72.67	0.64676		740
Synonymous	0.834	68	77.3	0.879	0.00000508	601
Loss of Function	1.58	4	9.15	0.437	4.75e-7	98

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000446	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Intolerance Scores

• loftool: 0.199
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.36

Haploinsufficiency Scores

• pHI: 0.795
• hipred: N
• hipred_score: 0.480
• ghis: 0.461

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.736

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem53

Gene ontology

• Cellular component: nucleus;integral component of membrane