DHODH

dihydroorotate dehydrogenase (quinone)

Basic information

Region (hg38): 16:72008588-72027664

Links

ENSG00000102967 ∙ NCBI:1723 ∙ OMIM:126064 ∙ HGNC:2867 ∙ Uniprot:Q02127 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• postaxial acrofacial dysostosis (Definitive), mode of inheritance: AR
• postaxial acrofacial dysostosis (Strong), mode of inheritance: AR
• postaxial acrofacial dysostosis (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Postaxial acrofacial dysostosis (Miller syndrome)	AR	General	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	Craniofacial; Musculoskeletal; Ophthalmologic	501501; 19915526; 21346561; 22692683

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DHODH gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DHODH gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	18		22
missense		2	46	3	3	54
nonsense	1	1	1			3
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	1		3
non coding			17	14	25	56
Total	1	4	69	35	28

Variants in DHODH

This is a list of pathogenic ClinVar variants found in the DHODH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-72008736-A-G		Miller syndrome	Benign/Likely benign (Dec 17, 2018)
16-72008770-G-A		DHODH-related disorder	Likely benign (Jul 31, 2019)
16-72008778-A-G		Miller syndrome	Uncertain significance (Jan 13, 2018)
16-72008779-C-T		DHODH-related disorder	Likely benign (Nov 27, 2019)
16-72008783-A-C		not specified • Miller syndrome	Benign (Jan 31, 2024)
16-72008926-T-G			Benign (Oct 16, 2018)
16-72009061-G-A			Benign (Jun 17, 2021)
16-72012039-C-T		Miller syndrome	Conflicting classifications of pathogenicity (Nov 14, 2022)
16-72012054-G-A			Uncertain significance (Dec 24, 2021)
16-72012084-G-A		Miller syndrome	Uncertain significance (Jan 22, 2016)
16-72012100-C-G		Miller syndrome	Uncertain significance (Jan 13, 2018)
16-72012100-C-T		Miller syndrome	Benign/Likely benign (Nov 18, 2023)
16-72012101-G-A		Miller syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 01, 2023)
16-72012118-C-A			Likely benign (Aug 18, 2017)
16-72012121-G-C		DHODH-related disorder	Likely benign (Sep 27, 2023)
16-72012123-G-T		Miller syndrome	Uncertain significance (-)
16-72012131-C-T		Inborn genetic diseases	Uncertain significance (Apr 23, 2024)
16-72012132-G-A		Miller syndrome	Uncertain significance (Feb 04, 2022)
16-72012132-GT-G		DHODH-related disorder	Uncertain significance (Mar 22, 2023)
16-72012168-G-A		Inborn genetic diseases	Uncertain significance (Jan 07, 2024)
16-72012181-G-A			Likely benign (Jun 23, 2017)
16-72012182-G-C		Miller syndrome	Uncertain significance (Jan 13, 2018)
16-72012206-C-G		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
16-72012207-G-A		Inborn genetic diseases	Uncertain significance (Feb 03, 2022)
16-72012216-C-T			Uncertain significance (Mar 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DHODH	protein_coding	protein_coding	ENST00000219240	9	16468

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00299	0.986	124852	0	59	124911	0.000236

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.337	254	239	1.06	0.0000162	2488
Missense in Polyphen		86	96.143	0.89451		1051
Synonymous	-1.41	117	99.1	1.18	0.00000669	871
Loss of Function	2.23	7	16.9	0.414	9.00e-7	203

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000255	0.000251
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000596	0.0000554
Finnish	0.0000928	0.0000927
European (Non-Finnish)	0.000406	0.000406
Middle Eastern	0.0000596	0.0000554
South Asian	0.000131	0.000131
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
• Disease: DISEASE: Postaxial acrofacial dysostosis (POADS) [MIM:263750]: POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases. {ECO:0000269|PubMed:19915526}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Pyrimidine Metabolism;UMP Synthase Deiciency (Orotic Aciduria);MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy);Beta Ureidopropionase Deficiency;Dihydropyrimidinase Deficiency;Pyrimidine metabolism;Metabolism of nucleotides;Pyrimidine biosynthesis;Metabolism;Nucleobase biosynthesis;Pyrimidine metabolism;Pyrimidine nucleotides nucleosides metabolism (Consensus)

Recessive Scores

• pRec: 0.439

Intolerance Scores

• loftool: 0.178
• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.31

Haploinsufficiency Scores

• pHI: 0.289
• hipred: N
• hipred_score: 0.267
• ghis: 0.425

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.940

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dhodh
• Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); skeleton phenotype; immune system phenotype

Gene ontology

• Biological process: 'de novo' pyrimidine nucleobase biosynthetic process;female pregnancy;lactation;pyrimidine ribonucleotide biosynthetic process;response to caffeine;response to starvation;positive regulation of apoptotic process;'de novo' UMP biosynthetic process;pyrimidine nucleoside biosynthetic process;oxidation-reduction process;regulation of mitochondrial fission;response to L-arginine
• Cellular component: nucleoplasm;mitochondrion;mitochondrial inner membrane;cytosol;plasma membrane;integral component of membrane;neuronal cell body
• Molecular function: dihydroorotate dehydrogenase activity;drug binding;FMN binding;ubiquinone binding