PKHD1L1

protein-coding

PKHD1 like 1, the group of IPT domain containing

Gene summary

Predicted to enable signaling receptor activity. Predicted to be involved in immune response. Predicted to act upstream of or within sensory perception of sound. Predicted to be located in cytosol; membrane; and obsolete extracellular space. Implicated in autosomal recessive nonsyndromic deafness. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_177531.6

Inheritance

ClinVar variants

P:22U:676B:70

Top phenotype

Deafness, autosomal recessive 124

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr8:109,362,461-109,537,207

External References & Databases

Ensembl (ENSG00000205038)

Transcript & Mutation Effects

hg38 • Region Span ~174.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive nonsyndromic hearing loss 124LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0968981

Submitter: Ambry Genetics

sensorineural hearing loss disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020678

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 124AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

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

Refs: 38459354

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PKHD1L1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 654

PKHD1L1-related disorderTotal: 67

not providedTotal: 32

Autosomal recessive nonsyndromic hearing loss 124Total: 25

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_177531.6. 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			6 clinvar	10 clinvar	2 clinvar	18
missense	2 clinvar	1 clinvar	653 clinvar	51 clinvar	4 clinvar	711
nonsense	1 clinvar	9 clinvar	4 clinvar	2 clinvar		16
start loss						0
frameshift	1 clinvar	7 clinvar	5 clinvar			13
splice donor/acceptor (+/-2bp)		1 clinvar	8 clinvar	1 clinvar		10
Total	4	18	676	64	6	768

Highest pathogenic variant AF is 0.00034767887

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_177531.6	RefSeq	NP_803875.2	78	MANE Select
ENST00000378402.10	Ensembl	ENSP00000367655.5	78	MANE Select
ENST00000526472.1	Ensembl	ENSP00000437376.1	24	Standard
ENST00000997388.1	Ensembl	ENSP00000667205.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

immune response

Molecular Function

signaling receptor activity

Cellular Component

extracellular space
cytosol
cilium
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378402
Coding exons: 78
Length: 167854
Individuals with no LoFs: 105692
Homozygous LoFs: 1486
Heterozygous LoFs: 17698
Defined: 124876
p: 0.0800

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.719	2145	2.05e+3	1.04	0.000100	27569
Missense (PolyPhen)		586	583.56	1.0042		7591
Synonymous	-0.630	757	735	1.03	0.0000383	8193
Loss of Function	0.857	174	187	0.932	0.00000959	2493

Population LoF Frequency

Population	CAF	p-value	Status
African	0.019	0.018	notable
Latino/Admixed American	0.27	0.25	notable
Ashkenazi Jewish	0.017	0.017	notable
East Asian	0.025	0.024	notable
Finnish	0.073	0.072	notable
European (Non-Finnish)	0.065	0.064	notable
South Asian	0.067	0.064	notable
Other	0.072	0.069	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.0530
RVIS EVS: 5.45
RVIS percentile EVS: 99.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.108

Gene Damage Prediction

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