TMEM135

protein-coding

transmembrane protein 135, the group of Tim17 family

Gene summary

Predicted to be involved in peroxisome organization. Predicted to act upstream of or within several processes, including regulation of oxidative phosphorylation; response to food; and retinal pigment epithelium development. Predicted to be located in peroxisome. Predicted to be active in peroxisomal membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_022918.4

Inheritance

ClinVar variants

U:51B:10

Top phenotype

TMEM135-related disorder

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr11:87,037,844-87,328,824

External References & Databases

Ensembl (ENSG00000166575)

Transcript & Mutation Effects

hg38 • Region Span ~291.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM135 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 45

TMEM135-related disorderTotal: 7

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022918.4. 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	2 clinvar	1 clinvar	4
missense			47 clinvar	4 clinvar	3 clinvar	54
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	51	6	4	61

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022918.4	RefSeq	NP_075069.3	15	MANE Select
ENST00000305494.6	Ensembl	ENSP00000306344.5	15	MANE Select
NM_001168724.2	RefSeq	NP_001162195.1	14	Standard
ENST00000340353.11	Ensembl	ENSP00000345513.6	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

peroxisome organization
response to cold
response to food
regulation of mitochondrial fission

Cellular Component

peroxisome
peroxisomal membrane
lipid droplet
integral component of membrane
mitochondrial membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000305494
Coding exons: 15
Length: 285915
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.56	177	246	0.720	0.0000117	3000
Missense (PolyPhen)		21	55.606	0.37766		681
Synonymous	-0.714	94	85.6	1.10	0.00000413	856
Loss of Function	3.92	5	27.0	0.185	0.00000130	348

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in mitochondrial metabolism by regulating the balance between mitochondrial fusion and fission. May act as a regulator of mitochondrial fission that promotes DNM1L-dependent fission through activation of DNM1L. May be involved in peroxisome organization. {ECO:0000250|UniProtKB:Q5U4F4, ECO:0000250|UniProtKB:Q9CYV5}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.673
RVIS EVS: 1
RVIS percentile EVS: 90.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0545

Gene Damage Prediction

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