Autosomal recessive nonsyndromic hearing loss 70

Summary

Autosomal recessive nonsyndromic hearing loss 70 (MONDO:0013978) is a disease caused by PNPT1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PNPT1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive nonsyndromic hearing loss 70
Mondo ID	MONDO:0013978
OMIM	614934
DOID	DOID:0110521
UMLS	C1824925
MedGen	760477
GARD	0022646
Is cancer (heuristic)	no

Also known as: autosomal recessive deafness 70 · autosomal recessive nonsyndromic deafness 70 · autosomal recessive nonsyndromic deafness caused by mutation in PNPT1 · autosomal recessive nonsyndromic deafness type 70 · deafness, autosomal recessive 70 · deafness, autosomal recessive type 70 · DFNB70 · PNPT1 autosomal recessive nonsyndromic deafness

Data availability: 34 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › hearing loss, autosomal recessive › autosomal recessive nonsyndromic hearing loss 70

Related subtypes (101): autosomal recessive nonsyndromic hearing loss 5, autosomal recessive nonsyndromic hearing loss 1A, autosomal recessive nonsyndromic hearing loss 2, autosomal recessive nonsyndromic hearing loss 3, autosomal recessive nonsyndromic hearing loss 4, autosomal recessive nonsyndromic hearing loss 6, autosomal recessive nonsyndromic hearing loss 7, autosomal recessive nonsyndromic hearing loss 9, autosomal recessive nonsyndromic hearing loss 8, autosomal recessive nonsyndromic hearing loss 12, autosomal recessive nonsyndromic hearing loss 15, autosomal recessive nonsyndromic hearing loss 18A, autosomal recessive nonsyndromic hearing loss 17, autosomal recessive nonsyndromic hearing loss 13, autosomal recessive nonsyndromic hearing loss 21, autosomal recessive nonsyndromic hearing loss 14, autosomal recessive nonsyndromic hearing loss 16, autosomal recessive nonsyndromic hearing loss 20, autosomal recessive nonsyndromic hearing loss 26, autosomal recessive nonsyndromic hearing loss 27, autosomal recessive nonsyndromic hearing loss 22, autosomal recessive nonsyndromic hearing loss 31, autosomal recessive nonsyndromic hearing loss 30, autosomal recessive nonsyndromic hearing loss 33, autosomal recessive nonsyndromic hearing loss 37, autosomal recessive nonsyndromic hearing loss 38, autosomal recessive nonsyndromic hearing loss 40, autosomal recessive nonsyndromic hearing loss 39, autosomal recessive nonsyndromic hearing loss 35, autosomal recessive nonsyndromic hearing loss 32, autosomal recessive nonsyndromic hearing loss 36, autosomal recessive nonsyndromic hearing loss 48, autosomal recessive nonsyndromic hearing loss 23, autosomal recessive nonsyndromic hearing loss 42, autosomal recessive nonsyndromic hearing loss 46, autosomal recessive nonsyndromic hearing loss 53, autosomal recessive nonsyndromic hearing loss 28, autosomal recessive nonsyndromic hearing loss 51, autosomal recessive nonsyndromic hearing loss 47, autosomal recessive nonsyndromic hearing loss 55, autosomal recessive nonsyndromic hearing loss 62, autosomal recessive nonsyndromic hearing loss 49, autosomal recessive nonsyndromic hearing loss 44, autosomal recessive nonsyndromic hearing loss 66, autosomal recessive nonsyndromic hearing loss 59, autosomal recessive nonsyndromic hearing loss 65, autosomal recessive nonsyndromic hearing loss 67, autosomal recessive nonsyndromic hearing loss 68, autosomal recessive nonsyndromic hearing loss 24, autosomal recessive nonsyndromic hearing loss 63, autosomal recessive nonsyndromic hearing loss 45, autosomal recessive nonsyndromic hearing loss 1B, autosomal recessive nonsyndromic hearing loss 71, autosomal recessive nonsyndromic hearing loss 77, autosomal recessive nonsyndromic hearing loss 25, autosomal recessive nonsyndromic hearing loss 79, autosomal recessive nonsyndromic hearing loss 84A, autosomal recessive nonsyndromic hearing loss 85, autosomal recessive nonsyndromic hearing loss 91, autosomal recessive nonsyndromic hearing loss 83, autosomal recessive nonsyndromic hearing loss 74, autosomal recessive nonsyndromic hearing loss 61, autosomal recessive nonsyndromic hearing loss 89, autosomal recessive nonsyndromic hearing loss 29, autosomal recessive nonsyndromic hearing loss 96, autosomal recessive nonsyndromic hearing loss 86, autosomal recessive nonsyndromic hearing loss 98, autosomal recessive nonsyndromic hearing loss 93, autosomal recessive nonsyndromic hearing loss 84B, autosomal recessive nonsyndromic hearing loss 18B, autosomal recessive nonsyndromic hearing loss 88, autosomal recessive nonsyndromic hearing loss 76, autosomal recessive nonsyndromic hearing loss 101, autosomal recessive nonsyndromic hearing loss 102, autosomal recessive nonsyndromic hearing loss 103, autosomal recessive nonsyndromic hearing loss 104, autosomal recessive nonsyndromic hearing loss 97, hearing loss, autosomal recessive 111, hearing loss, autosomal recessive 118, with cochlear aplasia, hearing loss, autosomal recessive 119, hearing loss, autosomal recessive 117, hearing loss, autosomal recessive 112, hearing loss, autosomal recessive 113, hearing loss, autosomal recessive 100, hearing loss, autosomal recessive 94, hearing loss, autosomal recessive 114, hearing loss, autosomal recessive 115, hearing loss, autosomal recessive 99, hearing loss, autosomal recessive 106, hearing loss, autosomal recessive 107, hearing loss, autosomal recessive 108, hearing loss, autosomal recessive 57, hearing loss, autosomal recessive 109, hearing loss, autosomal recessive 116, hearing loss, autosomal recessive 110, hearing loss, autosomal recessive 120, hearing loss, autosomal recessive 121, hearing loss, autosomal recessive 122, hearing loss, autosomal recessive 123, autosomal recessive nonsyndromic hearing loss 124, hearing loss, autosomal recessive 125

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

34 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 8 conflicting classifications of pathogenicity, 6 benign, 5 pathogenic, 2 likely pathogenic, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1034189	NM_033109.5(PNPT1):c.298-2A>T	PNPT1	Pathogenic	criteria provided, single submitter
1034190	NM_033109.5(PNPT1):c.918del (p.Val307fs)	PNPT1	Pathogenic	criteria provided, single submitter
1455027	NM_033109.5(PNPT1):c.1748dup (p.Glu584fs)	PNPT1	Pathogenic	criteria provided, single submitter
1705644	NM_033109.5(PNPT1):c.574C>T (p.Arg192Ter)	PNPT1	Pathogenic	criteria provided, multiple submitters, no conflicts
215010	NM_033109.5(PNPT1):c.1519G>T (p.Ala507Ser)	PNPT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
869396	NM_033109.5(PNPT1):c.1818T>G (p.Val606=)	PNPT1	Pathogenic	criteria provided, multiple submitters, no conflicts
3780459	NM_033109.5(PNPT1):c.984del (p.Pro329fs)	PNPT1	Likely pathogenic	criteria provided, single submitter
39802	NM_033109.5(PNPT1):c.1424A>G (p.Glu475Gly)	PNPT1	Likely pathogenic	criteria provided, single submitter
972896	NM_033109.5(PNPT1):c.137C>G (p.Ala46Gly)	LOC129933770	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1342762	NM_033109.5(PNPT1):c.40C>T (p.Arg14Trp)	PNPT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
209184	NM_033109.5(PNPT1):c.1592C>G (p.Thr531Arg)	PNPT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
209185	NM_033109.5(PNPT1):c.1525G>A (p.Val509Ile)	PNPT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
215008	NM_033109.5(PNPT1):c.688G>C (p.Glu230Gln)	PNPT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
805221	NM_033109.5(PNPT1):c.1925_1927del (p.Val642del)	PNPT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
972897	NM_033109.5(PNPT1):c.1619A>G (p.Asn540Ser)	PNPT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
996028	NM_033109.5(PNPT1):c.2213G>A (p.Arg738His)	PNPT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1015538	NM_033109.5(PNPT1):c.2039C>T (p.Ala680Val)	PNPT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031031	NM_033109.5(PNPT1):c.1676C>G (p.Ala559Gly)	PNPT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034187	NM_033109.5(PNPT1):c.2147A>G (p.Lys716Arg)	PNPT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1370924	NM_033109.5(PNPT1):c.1972C>T (p.His658Tyr)	PNPT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1482633	NM_033109.5(PNPT1):c.736A>G (p.Lys246Glu)	PNPT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1695433	NM_033109.5(PNPT1):c.2234T>C (p.Met745Thr)	PNPT1	Uncertain significance	criteria provided, single submitter
2582501	NM_033109.5(PNPT1):c.2106G>C (p.Met702Ile)	PNPT1	Uncertain significance	criteria provided, single submitter
2582536	NM_033109.5(PNPT1):c.393T>G (p.Ser131Arg)	PNPT1	Uncertain significance	criteria provided, single submitter
2582557	NM_033109.5(PNPT1):c.1176+439G>A	PNPT1	Uncertain significance	criteria provided, single submitter
2582577	NM_033109.5(PNPT1):c.2067C>T (p.Ile689=)	PNPT1	Uncertain significance	criteria provided, single submitter
3767958	NM_033109.5(PNPT1):c.548C>T (p.Pro183Leu)	PNPT1	Uncertain significance	criteria provided, single submitter
138735	NM_033109.5(PNPT1):c.1074-19A>G	PNPT1	Benign	criteria provided, multiple submitters, no conflicts
138737	NM_033109.5(PNPT1):c.1390C>A (p.Arg464=)	PNPT1	Benign	criteria provided, multiple submitters, no conflicts
138742	NM_033109.5(PNPT1):c.361A>G (p.Ile121Val)	PNPT1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PNPT1	Definitive	Autosomal recessive	hearing loss disorder	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PNPT1	Orphanet:101111	Spinocerebellar ataxia type 25
PNPT1	Orphanet:319514	Combined oxidative phosphorylation defect type 13
PNPT1	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PNPT1	HGNC:23166	ENSG00000138035	Q8TCS8	Polyribonucleotide nucleotidyltransferase 1, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PNPT1	Polyribonucleotide nucleotidyltransferase 1, mitochondrial	RNA-binding protein implicated in numerous RNA metabolic processes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PNPT1	Scaffold/PPI	no	2.7.7.8	ExoRNase_PH_dom1, S1_domain, KH_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ventricle myocardium	1
secondary oocyte	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PNPT1	258	ubiquitous	marker	left ventricle myocardium, secondary oocyte, tibialis anterior

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PNPT1	3,741

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PNPT1	Q8TCS8	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitochondrial RNA degradation	1	1631.4×	6e-04	PNPT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
RNA import into mitochondrion	1	16852.0×	6e-04	PNPT1
nuclear polyadenylation-dependent mRNA catabolic process	1	16852.0×	6e-04	PNPT1
mitochondrial RNA 5’-end processing	1	8426.0×	6e-04	PNPT1
mitochondrial mRNA catabolic process	1	5617.3×	6e-04	PNPT1
positive regulation of mitochondrial RNA catabolic process	1	5617.3×	6e-04	PNPT1
mitochondrial RNA 3’-end processing	1	5617.3×	6e-04	PNPT1
rRNA import into mitochondrion	1	5617.3×	6e-04	PNPT1
mitochondrial mRNA polyadenylation	1	4213.0×	6e-04	PNPT1
positive regulation of miRNA catabolic process	1	4213.0×	6e-04	PNPT1
mitochondrial RNA catabolic process	1	2808.7×	8e-04	PNPT1
regulation of cellular respiration	1	2808.7×	8e-04	PNPT1
regulation of cellular senescence	1	1404.3×	0.001	PNPT1
positive regulation of mRNA catabolic process	1	1203.7×	0.002	PNPT1
response to growth hormone	1	1123.5×	0.002	PNPT1
protein homotrimerization	1	991.3×	0.002	PNPT1
cellular response to interferon-beta	1	526.6×	0.003	PNPT1
response to cAMP	1	510.7×	0.003	PNPT1
liver regeneration	1	510.7×	0.003	PNPT1
mRNA catabolic process	1	495.6×	0.003	PNPT1
RNA catabolic process	1	455.5×	0.003	PNPT1
cellular response to oxidative stress	1	154.6×	0.007	PNPT1
mitochondrion organization	1	151.8×	0.007	PNPT1
protein homooligomerization	1	122.1×	0.009	PNPT1
mRNA processing	1	78.8×	0.013	PNPT1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PNPT1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PNPT1	2.7.7.8	polyribonucleotide nucleotidyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PNPT1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PNPT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.