FAHD2A

Summary

FAHD2A (fumarylacetoacetate hydrolase domain containing 2A, HGNC:24252) is a protein-coding gene on chromosome 2q11.1, encoding Oxaloacetate tautomerase FAHD2A, mitochondrial (Q96GK7). Tautomerase that converts enol-oxaloacetate, a strong inhibitor of succinate dehydrogenase, to the physiological keto form of oxaloacetate. It is a selective cancer dependency (DepMap: 21.0% of cell lines).

Enables oxaloacetate tautomerase activity. Involved in oxaloacetate metabolic process. Located in mitochondrion.

Source: NCBI Gene 51011 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 78 total
• Cancer dependency (DepMap): dependent in 21.0% of screened cell lines
• MANE Select transcript: NM_016044

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24252
Approved symbol	FAHD2A
Name	fumarylacetoacetate hydrolase domain containing 2A
Location	2q11.1
Locus type	gene with protein product
Status	Approved
Aliases	CGI-105
Ensembl gene	ENSG00000115042
Ensembl biotype	protein_coding
Entrez	51011

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 22 protein_coding, 2 retained_intron

ENST00000233379, ENST00000418606, ENST00000445649, ENST00000447036, ENST00000463940, ENST00000470100, ENST00000851837, ENST00000851838, ENST00000851839, ENST00000851840, ENST00000851841, ENST00000851842, ENST00000851843, ENST00000851844, ENST00000851845, ENST00000851846, ENST00000922174, ENST00000922175, ENST00000922176, ENST00000968030, ENST00000968031, ENST00000968032, ENST00000968033, ENST00000968034

RefSeq mRNA: 1 — MANE Select: NM_016044 NM_016044

CCDS: CCDS2014

Canonical transcript exons

ENST00000233379 — 8 exons

Exon	Start	End
ENSE00000820677	95412895	95416616
ENSE00001617561	95402708	95402872
ENSE00002433761	95406941	95407157
ENSE00002439865	95412677	95412764
ENSE00002458487	95410864	95411026
ENSE00002531133	95410527	95410586
ENSE00003485419	95412434	95412542
ENSE00003571707	95405553	95405803

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 96.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.3934 / max 150.5887, expressed in 1810 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21435	20.3934	1810

Top tissues by expression

253 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.96	gold quality
right lobe of thyroid gland	UBERON:0001119	95.04	gold quality
left lobe of thyroid gland	UBERON:0001120	94.89	gold quality
thyroid gland	UBERON:0002046	93.95	gold quality
minor salivary gland	UBERON:0001830	93.67	gold quality
apex of heart	UBERON:0002098	93.38	gold quality
body of pancreas	UBERON:0001150	93.12	gold quality
left testis	UBERON:0004533	92.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.47	gold quality
right testis	UBERON:0004534	92.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.31	gold quality
saliva-secreting gland	UBERON:0001044	92.22	gold quality
mouth mucosa	UBERON:0003729	91.73	gold quality
heart left ventricle	UBERON:0002084	91.67	gold quality
cerebellar hemisphere	UBERON:0002245	91.61	gold quality
body of stomach	UBERON:0001161	91.60	gold quality
cerebellar cortex	UBERON:0002129	91.60	gold quality
left ovary	UBERON:0002119	91.50	gold quality
cerebellar vermis	UBERON:0004720	91.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.26	gold quality
spinal cord	UBERON:0002240	91.19	gold quality
cerebellum	UBERON:0002037	91.16	gold quality
right atrium auricular region	UBERON:0006631	91.12	gold quality
tibial nerve	UBERON:0001323	91.11	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.05	gold quality
right ovary	UBERON:0002118	91.04	gold quality
cardiac ventricle	UBERON:0002082	91.00	gold quality
gastrocnemius	UBERON:0001388	90.94	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.72	gold quality
right frontal lobe	UBERON:0002810	90.71	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting FAHD2A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-4523	85.64	61.16	64

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 21.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• The X-ray structure of fumarylacetoacetate hydrolase family member FLJ36880 has been determined to 2.2 angstroms resolution employing the semi-automated high-throughput structural genomics approach. (PMID:15551868)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fahd2a	ENSMUSG00000027371
rattus_norvegicus	Fahd2a	ENSRNOG00000013974

Paralogs (3): FAH (ENSG00000103876), FAHD2B (ENSG00000144199), FAHD1 (ENSG00000180185)

Protein

Protein identifiers

Oxaloacetate tautomerase FAHD2A, mitochondrial — Q96GK7 (reviewed: Q96GK7)

Alternative names: Fumarylacetoacetate hydrolase domain-containing protein 2A

All UniProt accessions (3): Q96GK7, C9J5B6, C9JGM0

UniProt curated annotations — full annotation on UniProt →

Function. Tautomerase that converts enol-oxaloacetate, a strong inhibitor of succinate dehydrogenase, to the physiological keto form of oxaloacetate. It is thereby required to maximize aerobic respiration efficiency by preventing succinate dehydrogenase inhibition.

Subcellular location. Mitochondrion.

Cofactor. Requires a divalent metal cation for activity.

Similarity. Belongs to the FAH family.

RefSeq proteins (1): NP_057128* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011234	Fumarylacetoacetase-like_C	Domain
IPR036663	Fumarylacetoacetase_C_sf	Homologous_superfamily
IPR051121	FAH	Family

Pfam: PF01557

Catalyzed reactions (Rhea), 1 shown:

• oxaloacetate = enol-oxaloacetate (RHEA:16021)

UniProt features (7 total): binding site 3, transit peptide 1, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GK7-F1	92.63	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 159; 161; 190

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 85 (showing top): GOBP_OXALOACETATE_METABOLIC_PROCESS, PRAMOONJAGO_SOX4_TARGETS_DN, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, CAIRO_HEPATOBLASTOMA_DN, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, MODULE_207, GARY_CD5_TARGETS_UP, STEIN_ESRRA_TARGETS_UP, HAMAI_APOPTOSIS_VIA_TRAIL_UP, chr2q11, GOMF_INTRAMOLECULAR_OXIDOREDUCTASE_ACTIVITY, GOMF_ISOMERASE_ACTIVITY, LI_DCP2_BOUND_MRNA

GO Biological Process (1): oxaloacetate metabolic process (GO:0006107)

GO Molecular Function (5): metal ion binding (GO:0046872), oxaloacetate tautomerase activity (GO:0050163), catalytic activity (GO:0003824), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
dicarboxylic acid metabolic process	1
cation binding	1
intramolecular oxidoreductase activity, interconverting keto- and enol-groups	1
molecular_function	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1466 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAHD2A	CFAP20	Q9Y6A4	468
FAHD2A	FAH	P16930	422
FAHD2A	ANKRD39	Q53RE8	417
FAHD2A	FAM178B	Q8IXR5	417
FAHD2A	ZNF514	Q96K75	414
FAHD2A	WRNIP1	Q96S55	405
FAHD2A	VWA3B	Q502W6	370
FAHD2A	ANKRD36B	Q8N2N9	368
FAHD2A	CCDC85C	A6NKD9	348
FAHD2A	BOLA1	Q9Y3E2	348
FAHD2A	DHX40	Q8IX18	340
FAHD2A	ITPRIPL1	Q6GPH6	336
FAHD2A	VPS9D1	Q9Y2B5	328
FAHD2A	TBC1D32	Q96NH3	327
FAHD2A	KBTBD4	Q9NVX7	323

IntAct

29 interactions, top by confidence:

A	B	Type	Score
FAHD2A	FAHD2B	psi-mi:“MI:0915”(physical association)	0.670
CALR	FAHD2A	psi-mi:“MI:0915”(physical association)	0.560
DLST	FAHD2A	psi-mi:“MI:0915”(physical association)	0.560
FAHD2A	NEK7	psi-mi:“MI:0915”(physical association)	0.560
SOX2	PDLIM1	psi-mi:“MI:0914”(association)	0.530
TAS2R41	YKT6	psi-mi:“MI:0914”(association)	0.530
FAHD2A	DBT	psi-mi:“MI:0914”(association)	0.530
HMCES	FAHD2A	psi-mi:“MI:0915”(physical association)	0.400
FCGR2A	PLPBP	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ZNF287	TRIM24	psi-mi:“MI:0914”(association)	0.350
FCER1A	STX6	psi-mi:“MI:0914”(association)	0.350
SETX	NME2P1	psi-mi:“MI:0914”(association)	0.350
OMP	CST1	psi-mi:“MI:0914”(association)	0.350
LCN8	LRRC41	psi-mi:“MI:0914”(association)	0.350
CD7	PIK3R2	psi-mi:“MI:0914”(association)	0.350
FAHD2B	CHMP2A	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
SPANXN3	OGA	psi-mi:“MI:0914”(association)	0.350

BioGRID (65): FAHD2B (Affinity Capture-MS), DBT (Affinity Capture-MS), BOLA3 (Affinity Capture-MS), FAHD2A (Affinity Capture-MS), FAHD2A (Affinity Capture-MS), FAHD2A (Co-fractionation), FAHD2A (Co-fractionation), FAHD2A (Co-fractionation), FAHD2A (Co-fractionation), FAHD2A (Co-fractionation), FAHD2B (Affinity Capture-MS), BOLA3 (Affinity Capture-MS), DBT (Affinity Capture-MS), FAHD2A (Affinity Capture-MS), FAHD2A (Affinity Capture-MS)

ESM2 similar proteins: A0B3M8, A4JPX9, A6TAC6, A7ZI97, A7ZWZ7, A9ALD1, B1K3Y3, B1LIN5, B1Z1Y2, B2JQV8, B4EKX6, B5Z2Q5, B7L506, B7M2Z8, B7MPB7, B7N8Q7, B7NK05, C1DRI8, F1MLX0, I6Y276, O06724, O86042, P23107, P23149, P42270, P49156, P76004, P77608, Q0B628, Q10B63, Q13VU0, Q1BJJ1, Q1NEI7, Q2KIB0, Q39BA7, Q3Z556, Q47GC8, Q47HM0, Q49KF9, Q5RCX5

Diamond homologs: A0A3G9JYJ6, A0B3M8, A3AJ77, A9ALD1, B1K3Y3, B1Z1Y2, B2RYW9, B4EKX6, F1MLX0, I6Y276, O06724, O28058, O58377, O86042, P34673, P37352, Q0B628, Q0QFQ3, Q10B63, Q1BJJ1, Q1NEI7, Q2FIA7, Q2FZT4, Q2HJ98, Q2KIB0, Q2YWW3, Q39BA7, Q3TC72, Q46978, Q49WA8, Q4L4Y4, Q54BF3, Q59050, Q5HHB6, Q5HQJ3, Q5RCX5, Q5RDW0, Q6AYQ8, Q6GAV8, Q6GIC0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

78 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1156 predictions. Top by Δscore:

Variant	Effect	Δscore
2:95407135:T:TA	donor_gain	1.0000
2:95407136:G:GA	donor_gain	1.0000
2:95407157:GGT:G	donor_loss	1.0000
2:95407158:G:C	donor_loss	1.0000
2:95407159:T:A	donor_loss	1.0000
2:95411027:GT:G	donor_loss	1.0000
2:95411028:T:A	donor_loss	1.0000
2:95412427:A:AG	acceptor_gain	1.0000
2:95412428:T:G	acceptor_gain	1.0000
2:95412430:TCA:T	acceptor_loss	1.0000
2:95412431:CAGAT:C	acceptor_loss	1.0000
2:95412432:A:AG	acceptor_gain	1.0000
2:95412432:A:G	acceptor_loss	1.0000
2:95412433:G:GA	acceptor_gain	1.0000
2:95412433:GATC:G	acceptor_gain	1.0000
2:95412433:GATCC:G	acceptor_gain	1.0000
2:95412543:G:GG	donor_gain	1.0000
2:95402851:G:GT	donor_gain	0.9900
2:95406938:CAG:C	acceptor_gain	0.9900
2:95406939:A:AG	acceptor_gain	0.9900
2:95406939:AGA:A	acceptor_gain	0.9900
2:95406940:G:GG	acceptor_gain	0.9900
2:95406940:GAG:G	acceptor_gain	0.9900
2:95407153:GCCAG:G	donor_gain	0.9900
2:95410524:CAGG:C	acceptor_gain	0.9900
2:95410525:AGGA:A	acceptor_gain	0.9900
2:95410526:GGAG:G	acceptor_gain	0.9900
2:95410859:CATA:C	acceptor_loss	0.9900
2:95410861:TAGGC:T	acceptor_loss	0.9900
2:95410862:A:AG	acceptor_gain	0.9900

AlphaMissense

2048 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:95407092:T:C	F133L	0.998
2:95407094:C:A	F133L	0.998
2:95407094:C:G	F133L	0.998
2:95410967:A:T	K209I	0.998
2:95410915:A:C	S192R	0.997
2:95410917:T:A	S192R	0.997
2:95410917:T:G	S192R	0.997
2:95407037:T:A	N114K	0.996
2:95407037:T:G	N114K	0.996
2:95410910:A:T	D190V	0.996
2:95410910:A:C	D190A	0.995
2:95407025:T:G	C110W	0.994
2:95410968:A:C	K209N	0.994
2:95410968:A:T	K209N	0.994
2:95410981:T:C	F214L	0.994
2:95410983:C:A	F214L	0.994
2:95410983:C:G	F214L	0.994
2:95407100:G:C	K135N	0.993
2:95407100:G:T	K135N	0.993
2:95410540:A:T	E159V	0.993
2:95410954:T:A	W205R	0.993
2:95410954:T:C	W205R	0.993
2:95410967:A:C	K209T	0.992
2:95407095:A:C	S134R	0.991
2:95407097:C:A	S134R	0.991
2:95407097:C:G	S134R	0.991
2:95410911:C:A	D190E	0.991
2:95410911:C:G	D190E	0.991
2:95412714:G:T	G278W	0.991
2:95407049:C:A	H118Q	0.990

dbSNP variants (sampled 300 via entrez): RS1000135312 (2:95415173 G>T), RS1000401475 (2:95417628 C>T), RS1000507946 (2:95412121 T>C), RS1000562005 (2:95405970 A>G), RS1000594764 (2:95406301 T>C), RS1000839451 (2:95411850 A>G), RS1001185598 (2:95414562 G>A), RS1001239074 (2:95408653 G>A), RS1001270121 (2:95408901 A>T), RS1001422686 (2:95402606 G>A,C), RS1002001787 (2:95418585 C>G,T), RS1002075286 (2:95418807 A>G), RS1002113415 (2:95413271 G>A,C,T), RS1002274300 (2:95407472 C>T), RS1002591798 (2:95413515 G>A,C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, affects expression	2
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	decreases expression	1
quercitrin	decreases expression	1
trichostatin A	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
nickel sulfate	increases expression	1
hydroquinone	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
jinfukang	increases expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cocaine	affects expression	1
Ivermectin	decreases expression	1
Nickel	decreases expression	1
Tretinoin	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.