TMEM38B

transmembrane protein 38B

Basic information

Region (hg38): 9:105694541-105776629

Previous symbols: [ "C9orf87" ]

Links

ENSG00000095209 ∙ NCBI:55151 ∙ OMIM:611236 ∙ HGNC:25535 ∙ Uniprot:Q9NVV0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteogenesis imperfecta type 14 (Strong), mode of inheritance: AR
• osteogenesis imperfecta type 4 (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteogenesis imperfecta, type XIV	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	23316006
The use of bisphosphonates has been described in osteogenesis imperfecta, but it is unclear if an early (genomic) diagnosis would be advantageous

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM38B gene.

• not provided (4 variants)
• Osteogenesis imperfecta type 14 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM38B 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			1	24	1	26
missense			59	3	2	64
nonsense	4	1	1			6
start loss			2			2
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				3		3
non coding			1	22	15	38
Total	4	2	65	49	18

Highest pathogenic variant AF is 0.00000658

Variants in TMEM38B

This is a list of pathogenic ClinVar variants found in the TMEM38B region.

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

Position	Type	Phenotype	Significance	ClinVar
9-105694607-A-C			Benign (Jun 28, 2018)
9-105694651-G-A		not specified	Uncertain significance (May 11, 2022)
9-105694662-T-C			Uncertain significance (Apr 11, 2022)
9-105694663-G-A		not specified	Uncertain significance (Jan 20, 2023)
9-105694665-A-C		Inborn genetic diseases	Uncertain significance (Mar 22, 2023)
9-105694675-G-A			Pathogenic (Dec 18, 2022)
9-105694693-C-G			Likely benign (Jul 03, 2022)
9-105694697-T-C			Uncertain significance (Jul 17, 2023)
9-105694698-C-T		Inborn genetic diseases	Uncertain significance (May 28, 2024)
9-105694703-A-C			Uncertain significance (Aug 16, 2022)
9-105694717-CT-C		Osteogenesis imperfecta type 14	Likely pathogenic (May 09, 2024)
9-105694732-G-A			Likely benign (Jan 11, 2024)
9-105694733-C-T		Inborn genetic diseases	Uncertain significance (Jul 16, 2024)
9-105694740-T-G		Inborn genetic diseases	Uncertain significance (Nov 13, 2024)
9-105694746-C-T			Uncertain significance (Jun 27, 2022)
9-105694755-C-A			Uncertain significance (Jul 12, 2021)
9-105694763-C-A		Inborn genetic diseases	Uncertain significance (May 11, 2022)
9-105694772-G-A			Uncertain significance (Jun 20, 2022)
9-105694782-G-A			Likely benign (Sep 09, 2023)
9-105694786-G-T			Likely benign (Jul 23, 2023)
9-105694855-C-T			Likely benign (Sep 26, 2018)
9-105695074-G-A			Likely benign (Jun 16, 2018)
9-105705276-G-A			Benign (Aug 20, 2018)
9-105705326-A-G			Benign (Jun 14, 2018)
9-105705560-T-G			Likely benign (Jan 16, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM38B	protein_coding	protein_coding	ENST00000374692	6	82069

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0195	0.964	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0505	158	156	1.01	0.00000714	1888
Missense in Polyphen		39	49.602	0.78625		644
Synonymous	-0.836	68	59.8	1.14	0.00000310	568
Loss of Function	2.09	5	13.2	0.380	6.35e-7	151

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000185	0.000185
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000544	0.0000544
South Asian	0.000297	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Monovalent cation channel required for maintenance of rapid intracellular calcium release. May act as a potassium counter-ion channel that functions in synchronization with calcium release from intracellular stores. {ECO:0000250|UniProtKB:Q9DAV9}.
• Disease: DISEASE: Osteogenesis imperfecta 14 (OI14) [MIM:615066]: An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI14 is characterized by variable degrees of severity of multiple fractures and osteopenia, with normal teeth, sclerae, and hearing. Fractures first occur prenatally or by age 6 years. {ECO:0000269|PubMed:23054245, ECO:0000269|PubMed:23316006}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.549
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.27

Haploinsufficiency Scores

• pHI: 0.199
• hipred: N
• hipred_score: 0.266
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.641

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem38b
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: potassium ion transmembrane transport
• Cellular component: nucleus;integral component of membrane;nuclear membrane;sarcoplasmic reticulum membrane
• Molecular function: potassium channel activity