TMEM53

protein-coding

transmembrane protein 53

Gene summary

Involved in negative regulation of BMP signaling pathway; negative regulation of ossification; and regulation of nucleocytoplasmic transport. Located in nuclear membrane. Implicated in craniotubular dysplasia Ikegawa type. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_024587.4

Inheritance

ClinVar variants

P:2U:46B:4

Top phenotype

Craniotubular dysplasia, Ikegawa type

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr1:44,635,238-44,674,481

External References & Databases

Ensembl (ENSG00000126106)

Transcript & Mutation Effects

hg38 • Region Span ~39.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

skeletal dysplasiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0018230

Submitter: PanelApp Australia

craniotubular dysplasia, Ikegawa typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859226

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Craniotubular dysplasia, Ikegawa typeAR

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 33824347

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM53 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 45

Craniotubular dysplasia, Ikegawa typeTotal: 4

TMEM53-related disorderTotal: 3

TMEM53-related craniotubular dysplasiaTotal: 2

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024587.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			45 clinvar	3 clinvar		48
nonsense		1 clinvar				1
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	1	46	3	1	52

Highest pathogenic variant AF is 0.000006875631

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024587.4	RefSeq	NP_078863.2	3	MANE Select
ENST00000372237.8	Ensembl	ENSP00000361311.3	3	MANE Select
NM_001300746.2	RefSeq	NP_001287675.1	1	Standard
NM_001300747.2	RefSeq	NP_001287676.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

nucleus
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372237
Coding exons: 3
Length: 39318
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125746
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.01	149	188	0.793	0.0000131	1766
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.199
RVIS EVS: 0.13
RVIS percentile EVS: 63.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.736

Gene Damage Prediction

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