FOLH1

folate hydrolase 1, the group of M28 metallopeptidases

Basic information

Region (hg38): 11:49145091-49208638

Previous symbols: [ "FOLH" ]

Links

ENSG00000086205 ∙ NCBI:2346 ∙ OMIM:600934 ∙ HGNC:3788 ∙ Uniprot:Q04609 ∙ 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 FOLH1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOLH1 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				2		2
missense			29	2	3	34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	29	4	3

Variants in FOLH1

This is a list of pathogenic ClinVar variants found in the FOLH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-49146902-C-T		not specified	Uncertain significance (Mar 06, 2023)
11-49146925-C-T		not specified	Uncertain significance (Apr 11, 2023)
11-49148649-G-T		not specified	Uncertain significance (Jan 27, 2022)
11-49153885-G-T		not specified	Uncertain significance (Oct 17, 2023)
11-49154246-T-A		not specified	Uncertain significance (May 26, 2023)
11-49154258-G-T		not specified	Uncertain significance (Apr 05, 2023)
11-49154315-C-A		not specified	Uncertain significance (Feb 06, 2024)
11-49154401-T-C		not specified	Uncertain significance (Sep 14, 2023)
11-49154441-A-T		not specified	Uncertain significance (Aug 21, 2023)
11-49154468-G-C		not specified	Uncertain significance (May 26, 2023)
11-49156733-C-T		not specified	Uncertain significance (Jul 14, 2021)
11-49156734-G-A		not specified	Uncertain significance (Nov 21, 2023)
11-49156769-A-G		not specified	Uncertain significance (Jan 31, 2024)
11-49158015-C-T		not specified	Uncertain significance (Aug 02, 2021)
11-49158026-T-A		not specified	Uncertain significance (Dec 03, 2021)
11-49164707-C-G		not specified	Uncertain significance (Apr 08, 2022)
11-49169228-C-T		not specified	Uncertain significance (Aug 10, 2021)
11-49171214-C-T		not specified	Uncertain significance (Mar 07, 2024)
11-49173381-T-C		not specified	Uncertain significance (May 28, 2023)
11-49175940-G-A		not specified	Uncertain significance (May 06, 2022)
11-49183171-A-T		not specified	Uncertain significance (Apr 18, 2023)
11-49183228-G-T		not specified	Uncertain significance (Mar 23, 2022)
11-49185693-G-A			Likely benign (Dec 01, 2022)
11-49185731-C-T		not specified	Uncertain significance (Aug 28, 2023)
11-49185747-C-T		not specified	Uncertain significance (Apr 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOLH1	protein_coding	protein_coding	ENST00000256999	19	62036

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.20e-9	0.998	125682	0	63	125745	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.51	295	378	0.781	0.0000182	4878
Missense in Polyphen		98	155.02	0.63218		1960
Synonymous	0.184	128	131	0.979	0.00000644	1398
Loss of Function	2.84	20	39.2	0.510	0.00000197	509

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000858	0.000842
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.000329	0.000326
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000199	0.000193
Middle Eastern	0.000329	0.000326
South Asian	0.000167	0.000163
Other	0.000784	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has both folate hydrolase and N-acetylated-alpha-linked- acidic dipeptidase (NAALADase) activity. Has a preference for tri- alpha-glutamate peptides. In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N- aceylaspartylglutamate (NAAG), thereby releasing glutamate. Involved in prostate tumor progression.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Vitamin digestion and absorption - Homo sapiens (human);One Carbon Metabolism;Metabolism of amino acids and derivatives;Metabolism;Amino acid synthesis and interconversion (transamination) (Consensus)

Recessive Scores

• pRec: 0.432

Intolerance Scores

• loftool: 0.898
• rvis_EVS: 1.33
• rvis_percentile_EVS: 94.21

Haploinsufficiency Scores

• pHI: 0.158
• hipred: Y
• hipred_score: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.604

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Folh1
• Phenotype: homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: proteolysis;folic acid-containing compound metabolic process;cellular amino acid biosynthetic process;C-terminal protein deglutamylation
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;cell surface;membrane;extracellular exosome
• Molecular function: metallocarboxypeptidase activity;peptidase activity;dipeptidase activity;metal ion binding;Ac-Asp-Glu binding;tetrahydrofolyl-poly(glutamate) polymer binding