HKDC1

protein-coding

hexokinase domain containing 1

Gene summary

This gene encodes a member of the hexokinase protein family. The encoded protein is involved in glucose metabolism, and reduced expression may be associated with gestational diabetes mellitus. High expression of this gene may also be associated with poor prognosis in hepatocarcinoma. [provided by RefSeq, Sep 2016]

MANE transcript

NM_025130.4

Inheritance

ClinVar variants

P:8U:181B:17

Top phenotype

Retinitis pigmentosa 92

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr10:69,220,332-69,267,552

External References & Databases

Ensembl (ENSG00000156510)

Transcript & Mutation Effects

hg38 • Region Span ~47.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

retinitis pigmentosa 92LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030619

Submitter: PanelApp Australia

retinitis pigmentosaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019200

Submitter: G2P

Clinical Genomic Database (CGD)

Retinitis pigmentosa 92AR

Manifestation: Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30085091

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HKDC1 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 177

Retinitis pigmentosa 92Total: 13

not providedTotal: 9

Short statureTotal: 3

Nonsyndromic cleft lip palateTotal: 2

Long QT syndromeTotal: 1

Keratoconus 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025130.4. 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	6 clinvar	2 clinvar	11
missense		5 clinvar	174 clinvar	7 clinvar	1 clinvar	187
nonsense		1 clinvar	1 clinvar	1 clinvar		3
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar			3
Total	0	8	181	14	3	206

Highest pathogenic variant AF is 0.00014311682

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025130.4	RefSeq	NP_079406.4	18	MANE Select
ENST00000354624.6	Ensembl	ENSP00000346643.5	18	MANE Select
ENST00000953956.1	Ensembl	ENSP00000624015.1	17	Standard
ENST00000953956.2	Ensembl	ENSP00000624015.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

UDP-<i>N</i>-acetyl-D-galactosamine biosynthesis II
Glycolysis / Gluconeogenesis - Homo sapiens (human)
Fructose and mannose metabolism - Homo sapiens (human)
Central carbon metabolism in cancer - Homo sapiens (human)
Type II diabetes mellitus - Homo sapiens (human)

Biological Process

cellular glucose homeostasis
glycolytic process
hexose metabolic process
carbohydrate phosphorylation
glucose 6-phosphate metabolic process

Molecular Function

glucokinase activity
ATP binding
glucose binding
fructokinase activity
mannokinase activity

Cellular Component

mitochondrion
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354624
Coding exons: 18
Length: 47257
Individuals with no LoFs: 125586
Homozygous LoFs: 1
Heterozygous LoFs: 160
Defined: 125747
p: 0.000640

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.137	583	574	1.02	0.0000351	6016
Missense (PolyPhen)		205	222.61	0.9209		2355
Synonymous	0.276	231	236	0.977	0.0000159	1830
Loss of Function	2.18	29	44.7	0.648	0.00000273	478

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0017	0.0017	notable
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.0010	0.0010	notable
Finnish	0.00052	0.00051	rare
European (Non-Finnish)	0.00068	0.00064	rare
South Asian	0.00049	0.00046	rare
Other	0.00036	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.115

Intolerance Scores

RVIS EVS: 0.28
RVIS percentile EVS: 70.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.151

Gene Damage Prediction

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