TMEM222

protein-coding

transmembrane protein 222

Gene summary

Located in dendrite. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C1orf160

MANE transcript

NM_032125.3

Inheritance

ClinVar variants

P:5U:39B:7

Top phenotype

Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr1:27,322,145-27,336,400

External References & Databases

Ensembl (ENSG00000186501)

Transcript & Mutation Effects

hg38 • Region Span ~14.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with motor and speech delay and behavioral abnormalitiesDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0859176

Submitter: LiferaOmics

neurodevelopmental disorder with motor and speech delay and behavioral abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859176

Submitter: PanelApp Australia

neurodevelopmental disorder with motor and speech delay and behavioral abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859176

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with motor and speech delay and behavioral abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859176

Submitter: G2P

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with motor and speech delay and behavioral abnormalitiesAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 33824500

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM222 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 35

Neurodevelopmental disorder with motor and speech delay and behavioral abnormalitiesTotal: 8

not providedTotal: 5

TMEM222-related disorderTotal: 2

not specifiedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032125.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	3 clinvar	1 clinvar	5
missense	1 clinvar		36 clinvar	2 clinvar	1 clinvar	40
nonsense	1 clinvar					1
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	1 clinvar			3
Total	4	1	39	5	2	51

Highest pathogenic variant AF is 0.0000068157287

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032125.3	RefSeq	NP_115501.2	6	MANE Select
ENST00000374076.9	Ensembl	ENSP00000363189.4	6	MANE Select
ENST00000464720.5	Ensembl	ENSP00000419528.2	3	Standard
ENST00000464813.5	Ensembl	ENSP00000417853.2	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374076
Coding exons: 6
Length: 14241
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125746
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.436	111	125	0.890	0.00000740	1349
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00015	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00013	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000046	0.000044	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.228
RVIS EVS: -0.12
RVIS percentile EVS: 44.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.955

Gene Damage Prediction

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