TMEM222

transmembrane protein 222

Basic information

Region (hg38): 1:27322145-27336400

Previous symbols: [ "C1orf160" ]

Links

ENSG00000186501 ∙ NCBI:84065 ∙ OMIM:619469 ∙ HGNC:25363 ∙ Uniprot:Q9H0R3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with motor and speech delay and behavioral abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities	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	Craniofacial; Musculoskeletal; Neurologic	33824500

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM222 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM222 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			16	1	1	18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding			2			2
Total	0	0	18	2	2

Variants in TMEM222

This is a list of pathogenic ClinVar variants found in the TMEM222 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-27322194-C-G		not specified	Uncertain significance (Oct 31, 2024)
1-27322226-T-C		Inborn genetic diseases • Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities	Uncertain significance (Aug 05, 2024)
1-27322234-C-T		Inborn genetic diseases	Uncertain significance (Aug 30, 2022)
1-27322235-C-T		Inborn genetic diseases	Uncertain significance (May 23, 2023)
1-27322280-C-A		Inborn genetic diseases	Uncertain significance (Mar 20, 2023)
1-27322283-C-T		Inborn genetic diseases	Uncertain significance (Jun 26, 2024)
1-27322291-A-G		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
1-27322292-C-T		not specified	Uncertain significance (Oct 31, 2024)
1-27322304-A-C		Inborn genetic diseases	Uncertain significance (Jul 14, 2024)
1-27322384-G-T		Inborn genetic diseases	Uncertain significance (Oct 06, 2022)
1-27330728-T-TC		Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities	Pathogenic (Aug 10, 2021)
1-27330739-G-A		Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities	Pathogenic (Aug 10, 2021)
1-27332074-A-T		Inborn genetic diseases	Uncertain significance (Jun 05, 2024)
1-27332092-A-G		Inborn genetic diseases	Uncertain significance (Dec 04, 2024)
1-27332097-G-A		Inborn genetic diseases	Uncertain significance (Dec 03, 2024)
1-27333953-C-A		Inborn genetic diseases	Uncertain significance (Feb 28, 2022)
1-27333958-G-A		Inborn genetic diseases	Likely benign (Nov 05, 2021)
1-27333980-C-T		Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities	Pathogenic (Aug 10, 2021)
1-27333981-A-G		Inborn genetic diseases	Uncertain significance (Apr 24, 2023)
1-27333995-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
1-27334049-C-T		Inborn genetic diseases	Uncertain significance (Aug 28, 2024)
1-27334221-G-A		Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities	Uncertain significance (Apr 04, 2024)
1-27334243-G-A			Benign (May 01, 2023)
1-27334251-T-G		TMEM222-related disorder	Likely benign (Jun 27, 2022)
1-27334275-ACGT-A		Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities	Pathogenic (Aug 11, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM222	protein_coding	protein_coding	ENST00000374076	6	14241

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000394	0.386	125735	0	11	125746	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.436	111	125	0.890	0.00000740	1349
Missense in Polyphen		26	44.667	0.58209		471
Synonymous	0.801	44	51.3	0.858	0.00000349	385
Loss of Function	0.431	9	10.5	0.857	4.53e-7	125

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000180	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000130	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000462	0.0000439
Middle Eastern	0.000130	0.000109
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.228
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.89

Haploinsufficiency Scores

• pHI: 0.445
• hipred: N
• hipred_score: 0.329
• ghis: 0.579

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem222

Gene ontology

• Cellular component: integral component of membrane