FHIT

fragile histidine triad diadenosine triphosphatase, the group of MicroRNA protein coding host genes|Histidine triad superfamily

Basic information

Region (hg38): 3:59747277-61251459

Links

ENSG00000189283 ∙ NCBI:2272 ∙ OMIM:601153 ∙ HGNC:3701 ∙ Uniprot:P49789 ∙ 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 FHIT gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FHIT 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	1	3
missense			15	2		17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	15	5	1

Variants in FHIT

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

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

Position	Type	Phenotype	Significance	ClinVar
3-59752240-C-T		not specified	Uncertain significance (Oct 04, 2022)
3-59752244-C-T			Likely benign (Jan 08, 2018)
3-59752249-C-A		not specified	Uncertain significance (Feb 26, 2024)
3-59752258-C-T		not specified	Uncertain significance (Nov 20, 2023)
3-59922348-C-T		not specified	Likely benign (Feb 22, 2023)
3-59922353-T-C		not specified	Uncertain significance (May 11, 2022)
3-59922365-T-C		not specified	Uncertain significance (Jan 23, 2023)
3-59922393-G-A		FHIT-related disorder	Likely benign (Dec 28, 2022)
3-60014014-G-C		not specified	Uncertain significance (Feb 14, 2023)
3-60014041-T-C		not specified	Uncertain significance (Oct 04, 2024)
3-60014057-T-C		not specified	Uncertain significance (Jun 16, 2023)
3-60014062-A-C		not specified	Uncertain significance (Oct 12, 2022)
3-60014074-G-A		not specified	Uncertain significance (Jan 10, 2022)
3-60014104-C-T		not specified	Uncertain significance (May 08, 2023)
3-60014119-C-T		not specified	Uncertain significance (Nov 17, 2022)
3-60014140-C-T		not specified	Uncertain significance (Jan 26, 2023)
3-60014216-A-G		FHIT-related disorder	Likely benign (Apr 27, 2020)
3-60210809-G-T		Lip and oral cavity carcinoma	association (Jan 01, 2016)
3-60536894-G-A			Likely benign (May 17, 2018)
3-60536907-G-A		not specified	Uncertain significance (Apr 25, 2023)
3-60536925-G-T		not specified	Uncertain significance (Apr 05, 2023)
3-60536938-G-C		not specified	Uncertain significance (Nov 05, 2021)
3-60536957-C-A			Benign (Aug 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FHIT	protein_coding	protein_coding	ENST00000468189	5	1502098

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00571	0.739	125719	0	23	125742	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.06	120	91.4	1.31	0.00000557	964
Missense in Polyphen		45	30.796	1.4612		322
Synonymous	-1.20	43	34.1	1.26	0.00000213	284
Loss of Function	0.813	4	6.18	0.647	2.61e-7	75

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.00	0.00
South Asian	0.0000336	0.0000327
Other	0.000328	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. Can also hydrolyze P(1)-P(4)-bis(5'- adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP. Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5. Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways. Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis. Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity, it may in part come from the mitochondrial form, which sensitizes the low- affinity Ca(2+) transporters, enhancing mitochondrial calcium uptake. Functions as tumor suppressor. {ECO:0000269|PubMed:12574506, ECO:0000269|PubMed:15313915, ECO:0000269|PubMed:16407838, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:19622739, ECO:0000269|PubMed:8794732, ECO:0000269|PubMed:9323207}.
• Disease: DISEASE: Note=A chromosomal aberration involving FHIT has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation t(3;8)(p14.2;q24.1) with RNF139. Although the 3p14.2 breakpoint has been shown to interrupt FHIT in its 5-prime non-coding region, it is unlikely that FHIT is causally related to renal or other malignancies. {ECO:0000269|PubMed:15007172}.; DISEASE: Note=Associated with digestive tract cancers. Numerous tumor types are found to have aberrant forms of FHIT protein due to deletions in a coding region of chromosome 3p14.2 including the fragile site locus FRA3B. {ECO:0000269|PubMed:15007172}.
• Pathway: Non-small cell lung cancer - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Purine metabolism - Homo sapiens (human) (Consensus)

Intolerance Scores

• loftool: 0.175
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.31

Haploinsufficiency Scores

• pHI: 0.255
• hipred: N
• hipred_score: 0.489
• ghis: 0.520

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.978

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fhit
• Phenotype: homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); immune system phenotype; digestive/alimentary phenotype; neoplasm; 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)

Gene ontology

• Biological process: purine nucleotide metabolic process;nucleotide metabolic process;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;intrinsic apoptotic signaling pathway by p53 class mediator
• Cellular component: fibrillar center;cytoplasm;mitochondrion;cytosol;plasma membrane
• Molecular function: nucleotide binding;catalytic activity;protein binding;hydrolase activity;ubiquitin protein ligase binding;identical protein binding;bis(5'-adenosyl)-triphosphatase activity