TMCO1

transmembrane and coiled-coil domains 1

Basic information

Region (hg38): 1:165724292-165827755

Previous symbols: [ "TMCC4" ]

Links

ENSG00000143183 ∙ NCBI:54499 ∙ OMIM:614123 ∙ HGNC:18188 ∙ Uniprot:Q9UM00 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1 (Definitive), mode of inheritance: AR
• cerebrofaciothoracic dysplasia (Moderate), mode of inheritance: AR
• cerebrofaciothoracic dysplasia (Moderate), mode of inheritance: AR
• cerebrofaciothoracic dysplasia (Definitive), mode of inheritance: AR
• cerebrofaciothoracic dysplasia (Strong), mode of inheritance: AR
• cerebrofaciothoracic dysplasia (Supportive), mode of inheritance: AR
• craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1	AR	Renal	Individuals have been described with renal anomalies and/or vesicoureteral reflux, and surveillance and management may be helpful to preserve renal function	Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal	17351359; 20018682; 23320496; 24194475; 30556256; 31102500

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMCO1 gene.

• not provided (37 variants)
• Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1 (11 variants)
• Inborn genetic diseases (7 variants)
• See cases (2 variants)
• not specified (1 variants)
• 7 conditions (1 variants)
• 19 conditions (1 variants)
• TMCO1-related condition (1 variants)
• Cerebro facio thoracic dysplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMCO1 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	1	2
missense	1	1	11	1	1	15
nonsense	4					4
start loss						0
frameshift	1	4				5
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region	1		1	2	2	6
non coding				9	9	18
Total	6	5	12	11	11

Highest pathogenic variant AF is 0.0000198

Variants in TMCO1

This is a list of pathogenic ClinVar variants found in the TMCO1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-165728057-A-G		Inborn genetic diseases	Uncertain significance (Feb 17, 2024)
1-165728083-G-A			Likely benign (Sep 12, 2023)
1-165728095-GGC-G		7 conditions • See cases	Likely pathogenic (Dec 21, 2022)
1-165728104-G-A		Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1	Benign (Jan 28, 2024)
1-165728260-C-CT			Benign (Aug 21, 2019)
1-165743038-A-G			Likely benign (Apr 16, 2019)
1-165743172-G-A		19 conditions • Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1 • See cases • Cerebro facio thoracic dysplasia	Pathogenic (Oct 18, 2023)
1-165743177-G-A			Uncertain significance (Oct 25, 2022)
1-165743218-T-C			Likely benign (May 15, 2023)
1-165743244-G-A		Inborn genetic diseases	Pathogenic (Jul 20, 2017)
1-165743252-A-G			Uncertain significance (Dec 27, 2021)
1-165743263-G-T		Inborn genetic diseases	Pathogenic (Jun 06, 2017)
1-165743268-A-G		Inborn genetic diseases	Uncertain significance (Apr 07, 2022)
1-165743295-C-A		Inborn genetic diseases	Uncertain significance (Jun 03, 2022)
1-165743298-C-G		Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
1-165743318-G-A			Likely benign (Feb 14, 2023)
1-165743318-GA-G		not specified	Benign (Dec 11, 2019)
1-165743318-G-GA			Benign (Dec 31, 2019)
1-165751986-T-C			Benign (Mar 31, 2019)
1-165752066-T-C			Likely benign (Jul 28, 2020)
1-165752099-C-G		Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1	Pathogenic (Jan 15, 2014)
1-165752165-C-G			Uncertain significance (Jul 07, 2022)
1-165752166-G-A		Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1	Pathogenic (Feb 01, 2014)
1-165752176-T-C			Likely benign (Jun 29, 2022)
1-165752181-C-T		Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1	Benign/Likely benign (Dec 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMCO1	protein_coding	protein_coding	ENST00000367881	7	100961

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.41e-10	0.164	125668	0	79	125747	0.000314

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.03	96	129	0.745	0.00000626	1525
Missense in Polyphen		21	31.521	0.66621		419
Synonymous	-0.0660	46	45.4	1.01	0.00000220	483
Loss of Function	0.438	15	16.9	0.885	0.00000110	160

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000688	0.000667
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.0000972	0.0000924
European (Non-Finnish)	0.000445	0.000440
Middle Eastern	0.00	0.00
South Asian	0.000239	0.000229
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium-selective channel required to prevent calcium stores from overfilling, thereby playing a key role in calcium homeostasis (PubMed:27212239). In response to endoplasmic reticulum overloading, assembles into a homotetramer, forming a functional calcium-selective channel, regulating the calcium content in endoplasmic reticulum store (PubMed:27212239). {ECO:0000269|PubMed:27212239}.
• Disease: DISEASE: Glaucoma, primary open angle (POAG) [MIM:137760]: A complex and genetically heterogeneous ocular disorder characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. In some cases, POAG shows digenic inheritance involving mutations in CYP1B1 and MYOC genes. {ECO:0000269|PubMed:21532571, ECO:0000269|PubMed:22714896}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.113

Intolerance Scores

• rvis_EVS: 0.06
• rvis_percentile_EVS: 58

Haploinsufficiency Scores

• pHI: 0.217
• hipred: N
• hipred_score: 0.420
• ghis: 0.657

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: N
• gene_indispensability_score: 0.476

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmco1
• Phenotype: homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: ER overload response;endoplasmic reticulum calcium ion homeostasis;calcium ion transmembrane transport
• Cellular component: Golgi membrane;endoplasmic reticulum;integral component of endoplasmic reticulum membrane
• Molecular function: calcium channel activity