PMVK

Summary

PMVK (phosphomevalonate kinase, HGNC:9141) is a protein-coding gene on chromosome 1q21.3, encoding Phosphomevalonate kinase (Q15126). Catalyzes the reversible ATP-dependent phosphorylation of mevalonate 5-phosphate to produce mevalonate diphosphate and ADP, a key step in the mevalonic acid mediated biosynthesis of isopentenyl diphosphate and other polyisoprenoid metabolites. It is a selective cancer dependency (DepMap: 26.2% of cell lines).

This gene encodes a peroxisomal enzyme that is a member of the galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase (GHMP) family of ATP-dependent enzymes. The encoded protein catalyzes the conversion of mevalonate 5-phosphate to mevalonate 5-diphosphate, which is the fifth step in the mevalonate pathway of isoprenoid biosynthesis. Mutations in this gene are linked to certain types of porokeratosis including disseminated superficial porokeratosis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10654 — RefSeq curated summary.

At a glance

• Gene–disease (curated): porokeratosis 1, Mibelli type (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 15
• Clinical variants (ClinVar): 58 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 9
• Cancer dependency (DepMap): dependent in 26.2% of screened cell lines
• MANE Select transcript: NM_006556

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9141
Approved symbol	PMVK
Name	phosphomevalonate kinase
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	PMK, PMKA, HUMPMKI
Ensembl gene	ENSG00000163344
Ensembl biotype	protein_coding
OMIM	607622
Entrez	10654

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000368467, ENST00000885055, ENST00000885056, ENST00000885057, ENST00000885058, ENST00000885059, ENST00000940350, ENST00000940351

RefSeq mRNA: 4 — MANE Select: NM_006556 NM_001323011, NM_001323012, NM_001348696, NM_006556

CCDS: CCDS1073

Canonical transcript exons

ENST00000368467 — 5 exons

Exon	Start	End
ENSE00001073573	154929024	154929176
ENSE00001073575	154926354	154926483
ENSE00001073580	154932352	154932415
ENSE00001447194	154924740	154925265
ENSE00001447196	154936591	154936719

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 97.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7923 / max 161.0956, expressed in 1809 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14848	11.8560	1781
14849	6.1726	1713
14847	1.3409	910
14850	1.3244	899
14851	0.0986	26

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.54	gold quality
lower esophagus mucosa	UBERON:0035834	97.42	gold quality
right lobe of liver	UBERON:0001114	96.30	gold quality
adenohypophysis	UBERON:0002196	96.29	gold quality
nucleus accumbens	UBERON:0001882	96.16	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.92	gold quality
skin of abdomen	UBERON:0001416	95.87	gold quality
anterior cingulate cortex	UBERON:0009835	95.84	gold quality
cingulate cortex	UBERON:0003027	95.80	gold quality
skin of leg	UBERON:0001511	95.72	gold quality
pituitary gland	UBERON:0000007	95.66	gold quality
esophagus mucosa	UBERON:0002469	95.65	gold quality
right adrenal gland cortex	UBERON:0035827	95.55	gold quality
right atrium auricular region	UBERON:0006631	95.52	gold quality
right adrenal gland	UBERON:0001233	95.51	gold quality
caudate nucleus	UBERON:0001873	95.45	gold quality
right frontal lobe	UBERON:0002810	95.45	gold quality
amygdala	UBERON:0001876	95.44	gold quality
left adrenal gland	UBERON:0001234	95.32	gold quality
left adrenal gland cortex	UBERON:0035825	95.32	gold quality
prefrontal cortex	UBERON:0000451	95.11	gold quality
putamen	UBERON:0001874	95.10	gold quality
esophagus	UBERON:0001043	94.80	gold quality
zone of skin	UBERON:0000014	94.63	gold quality
adrenal cortex	UBERON:0001235	94.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.63	gold quality
heart left ventricle	UBERON:0002084	94.47	gold quality
spinal cord	UBERON:0002240	94.44	gold quality
cardiac atrium	UBERON:0002081	94.42	gold quality
cardiac ventricle	UBERON:0002082	94.21	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SREBF2

miRNA regulators (miRDB)

8 targeting PMVK, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-12127	97.93	66.67	793
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-6747-3P	97.73	64.84	1596

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• found an exclusive cytosolic localization of both endogenously expressed PMVK(in human fibroblasts, human liver, and HEK293 cells) and overexpressed PMVK. No indication of a peroxisomal localization was obtained. (PMID:14729858)
• Functional evaluation of conserved basic residues in PMVK is reported. (PMID:17902708)
• This is the first report of hPMK crystal structure that suggests a potential substrate binding site and a possible enzyme catalytic mechanism. (PMID:18618710)
• Binding of mevalonate 5-phosphate causes the phosphomevalonate kinase structure to compress (tau(c) = 13.5 nsec), whereas subsequent binding of Mg-ADP opens the structure up (tau(c) = 15.6 nsec). (PMID:18798562)
• Data indicate that exome sequencing revealed disseminated superficial porokeratosis (DSP)-associated mutations in phosphomevalonate kinase gene (PMVK). (PMID:27052676)
• CELF1 Selectively Regulates Alternative Splicing of DNA Repair Genes Associated With Cataract in Human Lens Cell Line. (PMID:36585568)
• CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection. (PMID:38036565)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pmvk	ENSDARG00000070798
mus_musculus	Pmvk	ENSMUSG00000027952
rattus_norvegicus	Pmvk	ENSRNOG00000020696
drosophila_melanogaster	Pmvk	FBGN0032811
caenorhabditis_elegans		WBGENE00009335

Protein

Protein identifiers

Phosphomevalonate kinase — Q15126 (reviewed: Q15126)

All UniProt accessions (2): Q15126, Q6FGV9

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible ATP-dependent phosphorylation of mevalonate 5-phosphate to produce mevalonate diphosphate and ADP, a key step in the mevalonic acid mediated biosynthesis of isopentenyl diphosphate and other polyisoprenoid metabolites.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Heart, liver, skeletal muscle, kidney, and pancreas. Lower level in brain, placenta and lung.

Disease relevance. Porokeratosis 1, multiple types (POROK1) [MIM:175800] A form of porokeratosis, a disorder of faulty keratinization characterized by one or more atrophic patches surrounded by a distinctive hyperkeratotic ridgelike border called the cornoid lamella. The keratotic lesions can progress to overt cutaneous neoplasms, typically squamous cell carcinomas. Multiple clinical variants of porokeratosis are recognized, including porokeratosis of Mibelli, linear porokeratosis, disseminated superficial actinic porokeratosis, palmoplantar porokeratosis, and punctate porokeratosis. Different clinical presentations can be observed among members of the same family. Individuals expressing more than one variant have also been reported. The disease is caused by variants affecting the gene represented in this entry.

Induction. By sterol.

Pathway. Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: step 2/3.

RefSeq proteins (4): NP_001309940, NP_001309941, NP_001335625, NP_006547* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005919	Pmev_kin_anim	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF04275

Enzyme classification (BRENDA):

• EC 2.7.4.2 — phosphomevalonate kinase (BRENDA: 15 organisms, 53 substrates, 29 inhibitors, 127 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.043–5.2	40
ADP	0.047–5.62	25
(R)-MEVALONATE 5-DIPHOSPHATE	0.007–1.55	14
(R)-MEVALONATE 5-PHOSPHATE	0.034–2.04	14
(R)-5-PHOSPHOMEVALONATE	0.012–2.04	13
(R)-5-DIPHOSPHOMEVALONATE	0.007–1.55	10
PHOSPHOMEVALONATE	0.0042–0.35	4
(R,S)-5-PHOSPHOMEVALONATE	0.19	1
5-PHOSPHOMEVALONATE	0.042	1
ADPBETAS	0.38	1
DIPHOSPHOMEVALONATE	0.012	1

Catalyzed reactions (Rhea), 1 shown:

• (R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + ADP (RHEA:16341)

UniProt features (44 total): mutagenesis site 15, helix 9, binding site 6, strand 5, turn 5, sequence variant 3, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3CH4	X-RAY DIFFRACTION	1.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15126-F1	92.70	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6): 17–23; 141; 170; 171; 176; 180

Mutagenesis-validated functional residues (15):

Position	Phenotype
17	approximately 8-fold decrease in vmax for mgatp and r-mvp. approximately 5-fold increase in km for mgatp and r-mvp.
18	approximately 85-fold decrease in vmax for mgatp and r-mvp. approximately 5-fold increase in km for mgatp and r-mvp.
19	approximately 9-fold decrease in vmax for mgatp and r-mvp. approximately 10-fold increase in km for mgatp and r-mvp.
22	approximately 100000-fold decrease in vmax for mgatp.
23	approximately 7-fold decrease in vmax for mgatp and r-mvp. approximately 10-fold increase in km for mgatp and 5-fold inc
48	approximately 1400-fold decrease in vmax for mgatp and r-mvp. approximately 3-fold increase in km for mgatp and r-mvp.
69	approximately 500-fold decrease in vmax for mgatp and r-mvp. approximately 3-fold increase in km for mgatp and r-mvp.
73	approximately 3000-fold decrease in vmax for mgatp and r-mvp. no change in km for mgatp and approximately 3-fold increas
84	approximately 10-fold decrease in vmax for mgatp and r-mvp. approximately 3-fold increase in km for mgatp and 50-fold in
93	almost no change in km and vmax for mgatp and r-mvp.
110	approximately 20000-fold decrease in vmax for mgatp.
111	approximately 65-fold decrease in vmax for mgatp and r-mvp. approximately 8-fold increase in km for mgatp and 60-fold in
130	approximately 4-fold decrease in vmax for mgatp and r-mvp. approximately 3-fold increase in km for mgatp and r-mvp.
138	approximately 3-fold decrease in vmax for mgatp and r-mvp. approximately 5-fold increase in km for mgatp and no change i
141	approximately 15-fold decrease in vmax for mgatp and r-mvp. approximately 50-fold increase in km for mgatp and approxima

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-9969896	Lanosterol biosynthesis
R-HSA-191273	Cholesterol biosynthesis

MSigDB gene sets: 212 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, CHEOK_RESPONSE_TO_MERCAPTOPURINE_DN, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_RESPONSE_TO_STEROL, GOBP_STEROID_BIOSYNTHETIC_PROCESS, KEGG_TERPENOID_BACKBONE_BIOSYNTHESIS, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (8): cholesterol biosynthetic process (GO:0006695), sterol biosynthetic process (GO:0016126), isopentenyl diphosphate biosynthetic process, mevalonate pathway (GO:0019287), response to cholesterol (GO:0070723), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203)

GO Molecular Function (6): phosphomevalonate kinase activity (GO:0004631), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): peroxisome (GO:0005777), cytosol (GO:0005829), membrane (GO:0016020), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Cholesterol biosynthesis	1
Metabolism of steroids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
sterol metabolic process	2
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
steroid biosynthetic process	1
acetyl-CoA metabolic process	1
isopentenyl diphosphate biosynthetic process	1
response to sterol	1
response to alcohol	1
primary metabolic process	1
steroid metabolic process	1
lipid biosynthetic process	1
lipid metabolic process	1
secondary alcohol metabolic process	1
kinase activity	1
phosphotransferase activity, phosphate group as acceptor	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
microbody	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1116 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PMVK	MVK	Q03426	919
PMVK	HMGCR	P04035	913
PMVK	MVD	P53602	912
PMVK	FDPS	P14324	836
PMVK	HMGCS1	Q01581	799
PMVK	IDI1	Q13907	799
PMVK	PEX7	O00628	780
PMVK	GGPS1	O95749	771
PMVK	HMGA1	P10910	763
PMVK	IDI2	Q9BXS1	760
PMVK	PEX5	P50542	746
PMVK	ACAT1	P24752	730
PMVK	FDFT1	P37268	730
PMVK	SQLE	Q14534	710
PMVK	HMGCS2	P54868	708

IntAct

74 interactions, top by confidence:

A	B	Type	Score
PMVK	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
ZNF177	PMVK	psi-mi:“MI:0915”(physical association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
FYTTD1	UBA6	psi-mi:“MI:0914”(association)	0.530
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
ARL6IP6	YKT6	psi-mi:“MI:0914”(association)	0.530
RDH12	NME2P1	psi-mi:“MI:0914”(association)	0.530
SCNM1	SNX3	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
	PMVK	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
SDHA	HMGB3	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350
SLC25A32	NEDD8-MDP1	psi-mi:“MI:0914”(association)	0.350
FGB	NME2	psi-mi:“MI:0914”(association)	0.350
MBD5	NME2P1	psi-mi:“MI:0914”(association)	0.350
SETD3	SNX3	psi-mi:“MI:0914”(association)	0.350

BioGRID (136): PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS), PMVK (Affinity Capture-MS)

ESM2 similar proteins: A1L1L6, A2A825, A6QL63, C9J798, O14908, O43374, O94844, O95278, O95294, Q0P5N6, Q15126, Q1LVW0, Q2HJF8, Q2TBH1, Q3UMR5, Q3UNW5, Q4R4U1, Q5E9M9, Q5R5F8, Q5ZIW1, Q5ZM73, Q5ZM83, Q66JN8, Q6DFV5, Q6GQW0, Q6IE70, Q6NVC5, Q6NYU2, Q7TSA0, Q7Z6G3, Q8BG51, Q8BGF7, Q8BHT7, Q8CIW5, Q8IXI1, Q8IXI2, Q8JZN7, Q8VCX6, Q91XQ2, Q923S8

Diamond homologs: Q15126, Q29081, Q2KIU2, Q9D1G2, Q9VIT2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

58 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	31
Likely benign	4
Benign	9

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
253041	NM_006556.4(PMVK):c.412C>T (p.Arg138Ter)	Pathogenic
253042	NM_006556.4(PMVK):c.550del (p.Asn183_Leu184insTer)	Pathogenic
1344669	NM_006556.4(PMVK):c.329G>A (p.Arg110Gln)	Likely pathogenic
1344671	NM_006556.4(PMVK):c.379C>T (p.Gln127Ter)	Likely pathogenic
4077434	NM_006556.4(PMVK):c.96-1G>A	Likely pathogenic

SpliceAI

1130 predictions. Top by Δscore:

Variant	Effect	Δscore
1:154925261:CACCC:C	acceptor_gain	1.0000
1:154925263:CCC:C	acceptor_gain	1.0000
1:154925264:CC:C	acceptor_gain	1.0000
1:154925264:CCC:C	acceptor_gain	1.0000
1:154925265:CC:C	acceptor_gain	1.0000
1:154925265:CCTA:C	acceptor_loss	1.0000
1:154925266:C:CC	acceptor_gain	1.0000
1:154926349:CTCA:C	donor_loss	1.0000
1:154926351:CAC:C	donor_loss	1.0000
1:154926352:A:AC	donor_gain	1.0000
1:154926353:C:CC	donor_gain	1.0000
1:154926353:C:CG	donor_loss	1.0000
1:154926353:CCTGG:C	donor_gain	1.0000
1:154926479:ACCAG:A	acceptor_gain	1.0000
1:154926480:CCAG:C	acceptor_gain	1.0000
1:154926480:CCAGC:C	acceptor_gain	1.0000
1:154926481:CAGC:C	acceptor_gain	1.0000
1:154926482:AG:A	acceptor_gain	1.0000
1:154926482:AGC:A	acceptor_loss	1.0000
1:154926483:GC:G	acceptor_loss	1.0000
1:154926484:C:CC	acceptor_gain	1.0000
1:154926485:T:A	acceptor_loss	1.0000
1:154926488:A:T	acceptor_gain	1.0000
1:154929022:AC:A	donor_gain	1.0000
1:154929023:CC:C	donor_gain	1.0000
1:154929056:T:TA	donor_gain	1.0000
1:154932416:C:CC	acceptor_gain	1.0000
1:154925262:ACCC:A	acceptor_gain	0.9900
1:154925263:CCCC:C	acceptor_gain	0.9900
1:154925266:C:T	acceptor_gain	0.9900

AlphaMissense

1249 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:154929129:C:A	K69N	0.983
1:154929129:C:G	K69N	0.983
1:154932367:C:A	K48N	0.982
1:154932367:C:G	K48N	0.982
1:154926410:A:T	V129D	0.970
1:154926473:T:A	D108V	0.968
1:154936620:C:A	K22N	0.965
1:154936620:C:G	K22N	0.965
1:154926475:A:C	S107R	0.964
1:154926475:A:T	S107R	0.964
1:154926477:T:G	S107R	0.964
1:154936639:C:T	G16D	0.960
1:154936632:C:A	R18S	0.957
1:154936632:C:G	R18S	0.957
1:154926472:G:C	D108E	0.955
1:154926472:G:T	D108E	0.955
1:154926404:A:T	V131D	0.953
1:154936625:C:A	G21W	0.953
1:154936633:C:A	R18M	0.953
1:154936639:C:A	G16V	0.953
1:154936622:T:G	K22Q	0.952
1:154936624:C:T	G21E	0.952
1:154929063:A:C	F91L	0.950
1:154929063:A:T	F91L	0.950
1:154929065:A:G	F91L	0.950
1:154936621:T:A	K22M	0.950
1:154926407:C:G	R130P	0.949
1:154929085:C:G	R84P	0.949
1:154936619:C:G	D23H	0.949
1:154926369:A:G	W143R	0.947

dbSNP variants (sampled 300 via entrez): RS1000333419 (1:154930214 C>T), RS1000435072 (1:154943245 A>G), RS1000437633 (1:154933772 G>A), RS1000574396 (1:154944610 C>T), RS1000630795 (1:154938305 C>G,T), RS1000681347 (1:154938589 C>T), RS1000922947 (1:154944346 A>G), RS1001010683 (1:154930555 G>A), RS1001180531 (1:154931002 T>C), RS1001332922 (1:154937268 A>C,G,T), RS1001643628 (1:154925962 C>T), RS1001874765 (1:154942099 C>T), RS1001881109 (1:154931330 G>A,C), RS1002249964 (1:154931044 C>T), RS1002440567 (1:154930689 C>A,T)

Disease associations

OMIM: gene MIM:607622 | disease phenotypes: MIM:175800

GenCC curated gene-disease

Disease	Classification	Inheritance
porokeratosis 1, Mibelli type	Definitive	Autosomal dominant
autoinflammatory syndrome	Moderate	Autosomal recessive
porokeratosis of Mibelli	Supportive	Autosomal dominant

Mondo (4): porokeratosis 1, Mibelli type (MONDO:0008290), linear porokeratosis (MONDO:0023246), autoinflammatory syndrome (MONDO:0019751), porokeratosis of Mibelli (MONDO:0019141)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000962	Hyperkeratosis
HP:0000989	Pruritus
HP:0000992	Cutaneous photosensitivity
HP:0001036	Parakeratosis
HP:0003621	Juvenile onset
HP:0008065	Aplasia/Hypoplasia of the skin
HP:0011462	Young adult onset
HP:0200044	Porokeratosis

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001499_1	Atrial fibrillation	2.000000e-14
GCST001942_19	Prostate cancer	2.000000e-08
GCST002223_6	HDL cholesterol	2.000000e-08
GCST003602_3	Inflammatory bowel disease	2.000000e-09
GCST004232_76	HDL cholesterol levels	3.000000e-08
GCST006061_123	Atrial fibrillation	5.000000e-59
GCST006061_124	Atrial fibrillation	1.000000e-57
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST008103_81	Bipolar disorder	1.000000e-06
GCST009325_77	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004341	body fat distribution

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Lanosterol biosynthesis pathway

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
(R)-5-diphosphomevalonate	Competitive	4.75	pKi
3-hydroxy-3-methyl-6-phosphohexanoic acid	Inhibition	3.84	pKi
cinnamic acid	Competitive	2.42	pKi
isoferulic acid	Competitive	2.41	pKi

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	3
Vorinostat	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
afimoxifene	decreases response to substance	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
phosphomevalonic acid	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Adenosine Triphosphate	increases hydrolysis	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Cadmium	increases abundance, increases expression	1
Hydralazine	increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Selenomethionine	affects expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1PV	Abcam K-562 PMVK KO	Cancer cell line	Female
CVCL_D2LH	Abcam Raji PMVK KO	Cancer cell line	Male
CVCL_WQ32	Abcam Jurkat PMVK KO	Cancer cell line	Male

Clinical trials (associated diseases)

4 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00442182	PHASE2	UNKNOWN	The Efficacy and Safety of ITF2357 in AIS
NCT00887939	Not specified	COMPLETED	Pathogenesis of Physical Induced Urticarial Syndromes
NCT03510442	Not specified	RECRUITING	Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still’s Disease, and Related Conditions
NCT06248957	Not specified	RECRUITING	SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION