PANK4

protein-coding

pantothenate kinase 4 (inactive), the group of Pantothenate kinase family

Gene summary

This gene encodes a protein belonging to the pantothenate kinase family. Pantothenate kinase is a key regulatory enzyme in the biosynthesis of coenzyme A (CoA) in bacteria and mammalian cells. It catalyzes the first committed step in the universal biosynthetic pathway leading to CoA and is itself subject to regulation through feedback inhibition by CoA. This family member is most abundant in muscle but is expressed in all tissues. [provided by RefSeq, Jul 2008]

MANE transcript

NM_018216.4

Inheritance

ClinVar variants

U:106B:12

Top phenotype

Cataract 49

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr1:2,508,537-2,526,597

External References & Databases

Ensembl (ENSG00000157881)

Transcript & Mutation Effects

hg38 • Region Span ~18.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataractLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005129

Submitter: G2P

cataract 49MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0030465

Submitter: PanelApp Australia

early-onset posterior polar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020378

Submitter: Orphanet

cataract 49LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030465

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Cataract 49AD

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: 30585370

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PANK4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 108

not providedTotal: 6

Cataract 49Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018216.4. 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			2 clinvar	9 clinvar		11
missense			100 clinvar	3 clinvar		103
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	106	12	0	118

Highest pathogenic variant AF is 0.000010120761

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018216.4	RefSeq	NP_060686.3	19	MANE Select
ENST00000378466.9	Ensembl	ENSP00000367727.5	19	MANE Select
ENST00000435556.8	Ensembl	ENSP00000421433.3	19	Standard
ENST00000435556.9	Ensembl	ENSP00000421433.3	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pantothenate and CoA biosynthesis - Homo sapiens (human)
Coenzyme A biosynthesis
Metabolism
Vitamin B5 (pantothenate) metabolism
Metabolism of water-soluble vitamins and cofactors

Biological Process

coenzyme A biosynthetic process
phosphorylation

Molecular Function

pantothenate kinase activity
ATP binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378466
Coding exons: 19
Length: 18068
Individuals with no LoFs: 125670
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125681
p: 0.0000438

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.42	362	517	0.701	0.0000355	5019
Missense (PolyPhen)		91	203.62	0.44691		2116
Synonymous	-2.13	280	238	1.18	0.0000188	1541
Loss of Function	4.89	6	38.9	0.154	0.00000191	443

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the physiological regulation of the intracellular CoA concentration. {ECO:0000250}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.0792
RVIS EVS: -0.97
RVIS percentile EVS: 8.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.957

Gene Damage Prediction

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