TTYH3

protein-coding

tweety family member 3, the group of Tweety family

Gene summary

This gene encodes a member of the tweety family of proteins. Members of this family function as chloride anion channels. The encoded protein functions as a calcium(2+)-activated large conductance chloride(-) channel. [provided by RefSeq, Jul 2008]

MANE transcript

NM_025250.3

Inheritance

—

ClinVar variants

U:97B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr7:2,631,961-2,664,802

External References & Databases

Ensembl (ENSG00000136295)

Transcript & Mutation Effects

hg38 • Region Span ~32.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TTYH3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 95

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025250.3. 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				3 clinvar		3
missense			95 clinvar	1 clinvar		96
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	97	4	0	101

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025250.3	RefSeq	NP_079526.1	14	MANE Select
ENST00000258796.12	Ensembl	ENSP00000258796.7	14	MANE Select
ENST00000400376.2	Ensembl	ENSP00000383227.2	3	Standard
ENST00000403167.5	Ensembl	ENSP00000385015.1	10	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

Biological Process

chloride transport
ion transmembrane transport
chloride transmembrane transport

Molecular Function

intracellular calcium activated chloride channel activity
chloride channel activity
volume-sensitive chloride channel activity

Cellular Component

plasma membrane
chloride channel complex
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000258796
Coding exons: 14
Length: 32852
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125706
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.807	291	332	0.875	0.0000224	3271
Missense (PolyPhen)		98	121.6	0.80594		1202
Synonymous	0.417	156	163	0.958	0.0000126	1057
Loss of Function	4.68	2	29.3	0.0682	0.00000143	305

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000052	0.000046	rare
European (Non-Finnish)	0.000028	0.000026	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable large-conductance Ca(2+)-activated chloride channel. May play a role in Ca(2+) signal transduction. {ECO:0000269|PubMed:15010458}.;

Recessive Scores

pRec: 0.132

Intolerance Scores

LoFtool: 0.324
RVIS EVS: -0.35
RVIS percentile EVS: 29.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.777

Gene Damage Prediction

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