DHFR2

dihydrofolate reductase 2

Basic information

Region (hg38): 3:94047836-94063389

Previous symbols: [ "DHFRP4", "DHFRL1" ]

Links

ENSG00000178700 ∙ NCBI:200895 ∙ OMIM:616588 ∙ HGNC:27309 ∙ Uniprot:Q86XF0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DHFR2 gene.

• Joubert syndrome 8 (63 variants)
• not provided (9 variants)
• not specified (5 variants)
• Inborn genetic diseases (5 variants)
• Joubert syndrome and related disorders (1 variants)
• Familial aplasia of the vermis (1 variants)
• Joubert syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DHFR2 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						0
missense						0
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding		1	33	34	2	70
Total	0	1	33	34	2

Variants in DHFR2

This is a list of pathogenic ClinVar variants found in the DHFR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-94049358-G-A		not specified	Benign/Likely benign (Mar 01, 2019)
3-94049386-T-C		Joubert syndrome 8	Likely benign (Jul 17, 2023)
3-94049389-T-C		not specified	Likely benign (Jul 10, 2017)
3-94049403-T-A		Joubert syndrome 8	Uncertain significance (Feb 04, 2022)
3-94049410-T-C		Joubert syndrome 8	Likely benign (May 01, 2023)
3-94049413-T-C		Joubert syndrome 8	Benign/Likely benign (Aug 23, 2023)
3-94049414-A-G		Joubert syndrome 8	Uncertain significance (Apr 20, 2021)
3-94049424-C-G		not specified • Joubert syndrome 8	Benign (Jan 31, 2024)
3-94049426-A-G		Joubert syndrome 8 • ARL13B-related disorder	Likely benign (Jan 26, 2024)
3-94049431-A-G		Joubert syndrome 8	Likely benign (Aug 31, 2022)
3-94049439-T-C		Joubert syndrome 8	Uncertain significance (Oct 04, 2022)
3-94049448-A-G		Joubert syndrome 8 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 23, 2022)
3-94049450-C-T		Joubert syndrome 8	Uncertain significance (Aug 20, 2020)
3-94049451-A-G		Joubert syndrome 8 • Inborn genetic diseases	Uncertain significance (Sep 01, 2022)
3-94049452-C-G		Joubert syndrome 8	Uncertain significance (Jul 23, 2022)
3-94049454-G-A		Joubert syndrome 8	Uncertain significance (Jan 03, 2020)
3-94049470-T-C		Joubert syndrome 8	Likely benign (Aug 04, 2021)
3-94049471-A-G		Joubert syndrome 8	Uncertain significance (Nov 01, 2022)
3-94049475-A-G		Joubert syndrome 8	Uncertain significance (Jun 06, 2021)
3-94049498-A-T		Joubert syndrome 8	Uncertain significance (Jul 19, 2022)
3-94049499-C-T		Joubert syndrome 8 • Inborn genetic diseases	Uncertain significance (Jul 15, 2022)
3-94049500-G-A		Joubert syndrome 8	Likely benign (Oct 05, 2023)
3-94049503-A-C			Likely benign (Aug 01, 2024)
3-94049506-C-T		Joubert syndrome 8	Likely benign (Sep 20, 2023)
3-94049513-C-G		Joubert syndrome 8	Uncertain significance (Apr 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DHFR2	protein_coding	protein_coding	ENST00000394221	1	15554

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.225	0.657	125603	0	4	125607	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.597	81	97.6	0.830	0.00000504	1243
Missense in Polyphen		30	31.131	0.96368		420
Synonymous	-0.830	42	35.7	1.18	0.00000208	336
Loss of Function	1.10	1	3.10	0.323	2.00e-7	38

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000882	0.00000880
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Binds its own mRNA and that of DHFR. {ECO:0000269|PubMed:21876184, ECO:0000269|PubMed:21876188}.
• Pathway: Folate biosynthesis - Homo sapiens (human);One carbon pool by folate - Homo sapiens (human);Trans-sulfuration and one carbon metabolism;One carbon metabolism and related pathways;Metabolism;Metabolism of folate and pterines;dTMP <i>de novo</i> biosynthesis (mitochondrial);Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Intolerance Scores

• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.82

Haploinsufficiency Scores

• pHI: 0.445
• hipred: N
• hipred_score: 0.216
• ghis: 0.563

Essentials

• essential_gene_gene_trap: N

Gene ontology

• Biological process: one-carbon metabolic process;thymidine biosynthetic process;dihydrofolate metabolic process;tetrahydrofolate metabolic process;tetrahydrofolate biosynthetic process;folic acid metabolic process;oxidation-reduction process
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial matrix
• Molecular function: mRNA binding;dihydrofolate reductase activity;NADP binding