TPRN

protein-coding

taperin

Gene summary

This locus encodes a sensory epithelial protein. It was defined by linkage analysis in three Pakistani families to lie between D9S1818 (centromeric) and D9SH6 (telomeric). Mutations at this locus have been associated with autosomal recessive deafness. [provided by RefSeq, Oct 2010]

Previous symbols:

C9orf75
DFNB79

MANE transcript

NM_001128228.3

Inheritance

ClinVar variants

P:34U:226B:139

Top phenotype

Deafness, autosomal recessive 79

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr9:137,191,617-137,204,193

External References & Databases

Ensembl (ENSG00000176058)

Transcript & Mutation Effects

hg38 • Region Span ~12.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive nonsyndromic hearing loss 79STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013215

Submitter: Labcorp Genetics (formerly Invitae)

nonsyndromic genetic hearing lossDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019497

Submitter: ClinGen

The TPRN gene has been associated with autosomal recessive non-syndromic hearing loss (ARNSHL) using the ClinGen Clinical Validity Framework as of 8/4/2017. This association was made using case-level data and experimental data). At least 7 unique variants (e.g. missense, frameshift, nonsense) have been reported in humans. TPRN was first associated with this disease in humans as early as 2010 (Khan et al.). Association is seen in at least 9 probands in 6 publications (PMID: 19603065, 20170898, 20170899, 23340767, 25129962). Variants in this gene segregated with disease in at least 20 additional family members. The mechanism for disease is homozygous loss of function. This gene-disease association is supported by expression studies, knockout mice models, biochemical function studies, and protein interaction (PMID: 20170899, 20170899, 27693694, 24285636). In summary, TPRN is definitively associated with autosomal recessive non-syndromic hearing loss. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Hearing Loss Working Group on 9/12/2017.

autosomal recessive nonsyndromic hearing loss 79STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013215

Submitter: PanelApp Australia

autosomal recessive nonsyndromic hearing loss 79DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013215

Submitter: G2P

hearing loss, autosomal recessiveSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: Orphanet

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 79AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 19603065; 20170898; 23340767

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TPRN variants in ClinVar

9 Conditions Cataloged

not providedTotal: 326

Inborn genetic diseasesTotal: 148

not specifiedTotal: 64

Autosomal recessive nonsyndromic hearing loss 79Total: 33

TPRN-related disorderTotal: 31

Rare genetic deafnessTotal: 5

Hearing loss, autosomal recessiveTotal: 1

Ear malformationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001128228.3. 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			8 clinvar	99 clinvar	3 clinvar	110
missense			218 clinvar	35 clinvar	2 clinvar	255
nonsense	5 clinvar	3 clinvar				8
start loss						0
frameshift	13 clinvar	13 clinvar				26
splice donor/acceptor (+/-2bp)						0
Total	18	16	226	134	5	399

Highest pathogenic variant AF is 0.00026548578

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001128228.3	RefSeq	NP_001121700.2	4	MANE Select
ENST00000409012.6	Ensembl	ENSP00000387100.4	4	MANE Select
ENST00000333046.8	Ensembl	ENSP00000327617.4	3	Standard
ENST00000961754.1	Ensembl	ENSP00000631813.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

sensory perception of sound
stereocilium maintenance

Molecular Function

molecular_function
protein binding
phosphatase binding

Cellular Component

stereocilium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409012
Coding exons: 4
Length: 12577
Individuals with no LoFs: 125525
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125563
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.497	307	283	1.08	0.0000168	4430
Missense (PolyPhen)		106	101.92	1.04		1292
Synonymous	-1.91	160	132	1.21	0.00000885	1613
Loss of Function	2.13	6	14.9	0.403	6.86e-7	209

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000058	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.00026	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.283

Gene Damage Prediction

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