TRPC4AP

protein-coding

transient receptor potential cation channel subfamily C member 4 associated protein, the group of Protein phosphatase 1 regulatory subunits|Armadillo like helical domain containing

Gene summary

Enables phosphatase binding activity and ubiquitin-like ligase-substrate adaptor activity. Involved in protein ubiquitination and ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in cytosol. Part of Cul4A-RING E3 ubiquitin ligase complex. Is active in Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C20orf188

MANE transcript

NM_015638.3

Inheritance

ClinVar variants

U:103B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr20:35,002,404-35,092,807

External References & Databases

Ensembl (ENSG00000100991)

Transcript & Mutation Effects

hg38 • Region Span ~90.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypothyroidismLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005420

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRPC4AP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 92

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015638.3. 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			2 clinvar	2 clinvar		4
missense			95 clinvar			95
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	103	2	0	105

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 136 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015638.3	RefSeq	NP_056453.1	19	MANE Select
ENST00000252015.3	Ensembl	ENSP00000252015.2	19	MANE Select
NM_199368.2	RefSeq	NP_955400.1	19	Standard
ENST00000451813.6	Ensembl	ENSP00000400614.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Stimuli-sensing channels
Ion channel transport
Transport of small molecules
TRP channels
TNFalpha

Biological Process

ubiquitin-dependent protein catabolic process
protein ubiquitination
hair follicle maturation
calcium ion transmembrane transport

Molecular Function

calcium channel activity
protein binding
phosphatase binding

Cellular Component

plasma membrane
Cul4A-RING E3 ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252015
Coding exons: 19
Length: 90468
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.22	368	440	0.836	0.0000244	5226
Missense (PolyPhen)		91	156.42	0.58176		1941
Synonymous	0.271	170	175	0.974	0.00000937	1557
Loss of Function	4.94	10	46.2	0.216	0.00000274	485

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control. The DCX(TRUSS) complex specifically mediates the polyubiquitination and subsequent degradation of MYC. Also participates in the activation of NFKB1 in response to ligation of TNFRSF1A, possibly by linking TNFRSF1A to the IKK signalosome. Involved in JNK activation via its interaction with TRAF2. Also involved in elevation of endoplasmic reticulum Ca(2+) storage reduction in response to CHRM1. {ECO:0000269|PubMed:20551172}.;

Recessive Scores

pRec: 0.116

Intolerance Scores

LoFtool: 0.0526
RVIS EVS: -1.26
RVIS percentile EVS: 5.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.870

Gene Damage Prediction

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