TMEM218

protein-coding

transmembrane protein 218

Gene summary

Predicted to be located in cilium and membrane. Implicated in Joubert syndrome. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001258244.2

Inheritance

ClinVar variants

P:4U:21B:3

Top phenotype

Joubert syndrome 39

gnomAD constraint

pLI —, LoF o/e 0.99

Max pathogenic AF

—

Genomic locus

chr11:125,094,389-125,111,763

External References & Databases

Ensembl (ENSG00000150433)

Transcript & Mutation Effects

hg38 • Region Span ~17.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ciliopathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: G2P

Joubert syndrome 39STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030454

Submitter: Labcorp Genetics (formerly Invitae)

Joubert syndrome 39STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030454

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Joubert syndrome 39AR

Manifestation: Musculoskeletal; Neurologic; 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: 33791682

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM218 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 17

Joubert syndrome 39Total: 4

not providedTotal: 3

Joubert syndromeTotal: 3

Meckel syndrome, type 4Total: 2

Retinal disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001258244.2. 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		3
missense	1 clinvar	2 clinvar	17 clinvar	1 clinvar		21
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	2	2	21	3	0	28

Highest pathogenic variant AF is 0.0001332768

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 177 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001258244.2	RefSeq	NP_001245173.1	3	MANE Select
ENST00000682305.1	Ensembl	ENSP00000506979.1	3	MANE Select
NM_001080546.3	RefSeq	NP_001074015.1	3	Standard
NM_001258238.2	RefSeq	NP_001245167.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

cilium
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000455225
Coding exons: 3
Length: 15262
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125745
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.744	47	63.7	0.738	0.00000378	710
Missense (PolyPhen)		18	23.152	0.77746		248
Synonymous	-0.145	32	31.0	1.03	0.00000192	268
Loss of Function	0.0276	4	4.06	0.985	2.57e-7	44

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in ciliary biogenesis or function. {ECO:0000250|UniProtKB:Q9CQ44}.;

Intolerance Scores

LoFtool: 0.485
RVIS EVS: 0.04
RVIS percentile EVS: 56.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.281

Gene Damage Prediction

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