TTYH2

protein-coding

tweety family member 2, 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, and may play a role in kidney tumorigenesis. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_032646.6

Inheritance

—

ClinVar variants

U:93B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr17:74,213,571-74,262,020

External References & Databases

Ensembl (ENSG00000141540)

Transcript & Mutation Effects

hg38 • Region Span ~48.4 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 TTYH2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 91

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032646.6. 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	4 clinvar		5
missense			88 clinvar	4 clinvar		92
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	93	8	0	101

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032646.6	RefSeq	NP_116035.5	14	MANE Select
ENST00000269346.9	Ensembl	ENSP00000269346.4	14	MANE Select
NM_001330453.2	RefSeq	NP_001317382.1	14	Standard
NM_052869.1	RefSeq	NP_443101.1	6	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 transmembrane transport

Molecular Function

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

Cellular Component

plasma membrane
chloride channel complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269346
Coding exons: 14
Length: 48503
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.356	311	329	0.945	0.0000192	3452
Missense (PolyPhen)		73	90.526	0.8064		1056
Synonymous	-0.152	155	153	1.02	0.0000106	1093
Loss of Function	3.02	12	29.8	0.402	0.00000138	309

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000099	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

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

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.517
RVIS EVS: 0.83
RVIS percentile EVS: 88.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.521

Gene Damage Prediction

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