TMEM216

transmembrane protein 216

Basic information

Region (hg38): 11:61392392-61398866

Previous symbols: [ "CORS2", "MKS2" ]

Links

ENSG00000187049 ∙ NCBI:51259 ∙ OMIM:613277 ∙ HGNC:25018 ∙ Uniprot:Q9P0N5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 2 (Strong), mode of inheritance: AR
• Meckel syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome with oculorenal defect (Supportive), mode of inheritance: AR
• orofaciodigital syndrome type 6 (Supportive), mode of inheritance: AR
• Joubert syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 2; Meckel syndrome 2	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	Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	20036350; 20512146
Conditions may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial;

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM216 gene.

• Familial aplasia of the vermis (179 variants)
• Joubert syndrome 2 (73 variants)
• not provided (43 variants)
• Meckel syndrome, type 2 (41 variants)
• Meckel syndrome, type 2;Joubert syndrome 2 (17 variants)
• not specified (13 variants)
• Inborn genetic diseases (10 variants)
• Joubert syndrome 2;Meckel syndrome, type 2 (3 variants)
• TMEM216-related condition (2 variants)
• TMEM216-Related Disorders (2 variants)
• Meckel-Gruber syndrome (2 variants)
• Joubert syndrome 1 (1 variants)
• Abnormality of the nervous system (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM216 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				42	1	43
missense	1	1	39			41
nonsense	4	5				9
start loss			6			6
frameshift	6	10	1			17
inframe indel						0
splice donor/acceptor (+/-2bp)	1	10				11
splice region		1	8	12		21
non coding		2	23	38	6	69
Total	12	28	69	80	7

Highest pathogenic variant AF is 0.000131

Variants in TMEM216

This is a list of pathogenic ClinVar variants found in the TMEM216 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-61392497-T-C		Joubert syndrome 2 • Meckel syndrome, type 2	Conflicting classifications of pathogenicity (Jan 12, 2018)
11-61392504-A-C		Joubert syndrome 2 • Meckel syndrome, type 2	Uncertain significance (Jan 13, 2018)
11-61392541-G-A		Joubert syndrome 2 • Meckel syndrome, type 2	Conflicting classifications of pathogenicity (Jan 12, 2018)
11-61392546-G-A		Joubert syndrome 2 • Meckel syndrome, type 2	Conflicting classifications of pathogenicity (Jan 01, 2023)
11-61392604-G-T		TMEM216-related disorder	Likely benign (Apr 07, 2021)
11-61392606-TGCTCCGGGAGCCGCTGTGGCAGCGTATGCTGCCACG-T		Familial aplasia of the vermis	Uncertain significance (Jan 27, 2020)
11-61392608-C-G		not specified • Joubert syndrome 2 • Meckel syndrome, type 2	Benign/Likely benign (Jan 13, 2018)
11-61392608-C-T		Joubert syndrome 2 • Meckel syndrome, type 2 • not specified • TMEM216-related disorder	Conflicting classifications of pathogenicity (May 25, 2021)
11-61392621-TGTGGCAGCGTATGCTGCCAC-T		Meckel syndrome, type 2;Joubert syndrome 2	Uncertain significance (Mar 27, 2018)
11-61392626-C-T		TMEM216-related disorder	Likely benign (May 26, 2023)
11-61392630-G-T		not specified • Familial aplasia of the vermis • Meckel syndrome, type 2 • Joubert syndrome 2	Benign (Jul 19, 2022)
11-61392632-A-G		Meckel syndrome, type 2;Joubert syndrome 2	Uncertain significance (Mar 27, 2018)
11-61392633-T-A		Meckel syndrome, type 2;Joubert syndrome 2 • Familial aplasia of the vermis	Uncertain significance (Aug 16, 2022)
11-61392633-T-C		Meckel syndrome, type 2;Joubert syndrome 2	Uncertain significance (Mar 27, 2018)
11-61392635-C-G		Familial aplasia of the vermis	Uncertain significance (May 19, 2021)
11-61392635-C-T		Familial aplasia of the vermis	Conflicting classifications of pathogenicity (Aug 01, 2022)
11-61392636-T-C		Meckel syndrome, type 2 • Familial aplasia of the vermis • Joubert syndrome 2 • TMEM216-related disorder	Conflicting classifications of pathogenicity (Jan 27, 2024)
11-61392637-G-A		Familial aplasia of the vermis	Likely benign (Sep 04, 2023)
11-61392638-C-A		Joubert syndrome 2 • Familial aplasia of the vermis	Uncertain significance (Jun 27, 2022)
11-61392642-G-A		Familial aplasia of the vermis • Joubert syndrome 2 • Inborn genetic diseases	Uncertain significance (Mar 13, 2023)
11-61392645-G-T		Familial aplasia of the vermis	Uncertain significance (Oct 18, 2022)
11-61392647-C-G		Familial aplasia of the vermis	Uncertain significance (Jun 03, 2022)
11-61392647-C-T		Familial aplasia of the vermis	Likely benign (Dec 23, 2021)
11-61392653-A-G		Familial aplasia of the vermis	Uncertain significance (Aug 13, 2022)
11-61392657-C-T		Joubert syndrome 2 • Familial aplasia of the vermis • Inborn genetic diseases	Uncertain significance (Apr 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM216	protein_coding	protein_coding	ENST00000515837	5	7177

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00189	0.742	7894	86544	30200	124638	0.748

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.491	66	78.2	0.844	0.00000397	911
Missense in Polyphen		26	27.714	0.93816		347
Synonymous	0.995	25	32.2	0.777	0.00000160	310
Loss of Function	0.880	5	7.62	0.656	4.07e-7	84

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	1.21	1.20
Ashkenazi Jewish	0.891	0.830
East Asian	0.962	0.908
Finnish	0.877	0.826
European (Non-Finnish)	0.849	0.792
Middle Eastern	0.962	0.908
South Asian	0.835	0.780
Other	0.854	0.797

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition. {ECO:0000269|PubMed:22282472}.
• Disease: DISEASE: Joubert syndrome 2 (JBTS2) [MIM:608091]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. {ECO:0000269|PubMed:20036350, ECO:0000269|PubMed:20512146, ECO:0000269|PubMed:22282472, ECO:0000269|PubMed:22425360}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Meckel syndrome 2 (MKS2) [MIM:603194]: A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. {ECO:0000269|PubMed:20512146}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.113

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.156
• ghis: 0.411

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.921

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem216

Zebrafish Information Network

• Gene name: tmem216
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: cilium assembly;ciliary basal body-plasma membrane docking;non-motile cilium assembly
• Cellular component: cytosol;cytoskeleton;cilium;integral component of membrane;ciliary transition zone;MKS complex
• Molecular function: protein binding