MVD

protein-coding

mevalonate diphosphate decarboxylase

Gene summary

The enzyme mevalonate pyrophosphate decarboxylase catalyzes the conversion of mevalonate pyrophosphate into isopentenyl pyrophosphate in one of the early steps in cholesterol biosynthesis. It decarboxylates and dehydrates its substrate while hydrolyzing ATP. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002461.3

Inheritance

ClinVar variants

P:7U:100B:21

Top phenotype

Porokeratosis 7, multiple types

gnomAD constraint

pLI —, LoF o/e 1.21

Max pathogenic AF

—

Genomic locus

chr16:88,651,935-88,663,161

External References & Databases

Ensembl (ENSG00000167508)

Transcript & Mutation Effects

hg38 • Region Span ~11.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

porokeratosis 7, multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013868

Submitter: G2P

nonsyndromic genetic hearing lossSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0019497

Submitter: PanelApp Australia

porokeratosis 7, multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013868

Submitter: Labcorp Genetics (formerly Invitae)

porokeratosis 7, multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013868

Submitter: Genomics England PanelApp

disseminated superficial actinic porokeratosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019212

Submitter: Orphanet

Clinical Genomic Database (CGD)

Porokeratosis 7, multiple typesAD

Manifestation: Dermatologic

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: 22983302

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MVD variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 104

Porokeratosis 7, multiple typesTotal: 14

not providedTotal: 13

MVD-related disorderTotal: 9

Linear porokeratosisTotal: 2

Nonsyndromic hearing impairmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002461.3. 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			1 clinvar	11 clinvar	1 clinvar	13
missense		2 clinvar	95 clinvar	8 clinvar	1 clinvar	106
nonsense						0
start loss			1 clinvar			1
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)	2 clinvar	2 clinvar	2 clinvar			6
Total	2	5	100	19	2	128

Highest pathogenic variant AF is 0.0033370098

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002461.3	RefSeq	NP_002452.1	10	MANE Select
ENST00000301012.8	Ensembl	ENSP00000301012.3	10	MANE Select
ENST00000565610.5	Ensembl	ENSP00000456465.1	2	Standard
ENST00000567064.5	Ensembl	ENSP00000458049.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mevalonate pathway
Terpenoid backbone biosynthesis - Homo sapiens (human)
Simvastatin Action Pathway
Pravastatin Action Pathway
Atorvastatin Action Pathway

Biological Process

dolichyl diphosphate biosynthetic process
cholesterol biosynthetic process
positive regulation of cell population proliferation
isoprenoid biosynthetic process
isopentenyl diphosphate biosynthetic process, mevalonate pathway

Molecular Function

diphosphomevalonate decarboxylase activity
ATP binding
Hsp70 protein binding
protein homodimerization activity

Cellular Component

peroxisome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000301012
Coding exons: 10
Length: 11227
Individuals with no LoFs: 125657
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 125708
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.363	286	269	1.06	0.0000188	2502
Missense (PolyPhen)		80	81.565	0.98081		778
Synonymous	-1.20	136	119	1.14	0.00000862	838
Loss of Function	-0.862	23	18.9	1.21	9.87e-7	202

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.00036	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00010	0.000097	rare
South Asian	0.00087	0.00082	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Performs the first committed step in the biosynthesis of isoprenes.;

Recessive Scores

pRec: 0.198

Intolerance Scores

RVIS EVS: -1.06
RVIS percentile EVS: 7.52

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.999

Gene Damage Prediction

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