TMEM138

transmembrane protein 138

Basic information

Region (hg38): 11:61361964-61377890

Links

ENSG00000149483 ∙ NCBI:51524 ∙ OMIM:614459 ∙ HGNC:26944 ∙ Uniprot:Q9NPI0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome with oculorenal defect (Supportive), mode of inheritance: AR
• Joubert syndrome 16 (Moderate), mode of inheritance: AR
• Joubert syndrome 16 (Strong), mode of inheritance: AR
• Joubert syndrome 16 (Strong), mode of inheritance: AR
• ciliopathy (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 16	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	Musculoskeletal; Neurologic; Ophthalmologic; Renal	22282472; 20301500
The condition 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 TMEM138 gene.

• Joubert_syndrome_16 (137 variants)
• not_provided (31 variants)
• Inborn_genetic_diseases (13 variants)
• not_specified (7 variants)
• TMEM138-related_disorder (4 variants)
• Joubert_syndrome_and_related_disorders (2 variants)
• Meckel-Gruber_syndrome (1 variants)
• Joubert_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM138 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016464.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				24	1	25
missense	1	4	64	3		72
nonsense	3		1			4
start loss						0
frameshift	2	6	4			12
splice donor/acceptor (+/-2bp)		2				2
Total	6	12	69	27	1

Highest pathogenic variant AF is 0.0000223073

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM138	protein_coding	protein_coding	ENST00000278826	4	7509

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0470	0.864	125734	0	13	125747	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.473	75	87.4	0.858	0.00000456	1069
Missense in Polyphen		26	32.992	0.78806		423
Synonymous	-0.165	36	34.8	1.04	0.00000174	312
Loss of Function	1.40	3	7.00	0.429	2.97e-7	79

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000703	0.0000703
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for ciliogenesis. {ECO:0000269|PubMed:22282472}.
• Disease: DISEASE: Joubert syndrome 16 (JBTS16) [MIM:614465]: An autosomal recessive disorder characterized by oculomotor apraxia, variable coloboma, and rare kidney involvement. Neuroradiologically, it is characterized by 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 polydactyly. {ECO:0000269|PubMed:22282472}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.302
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.42

Haploinsufficiency Scores

• pHI: 0.0587
• hipred: N
• hipred_score: 0.247
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.132

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem138

Gene ontology

• Biological process: cilium assembly
• Cellular component: vacuolar membrane;cilium;integral component of membrane