FAHD2B

Summary

FAHD2B (fumarylacetoacetate hydrolase domain containing 2B, HGNC:25318) is a protein-coding gene on chromosome 2q11.2, encoding Oxaloacetate tautomerase FAHD2B, mitochondrial (Q6P2I3). Tautomerase that converts enol-oxaloacetate, a strong inhibitor of succinate dehydrogenase, to the physiological keto form of oxaloacetate.

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

Source: NCBI Gene 151313 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_001320848

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25318
Approved symbol	FAHD2B
Name	fumarylacetoacetate hydrolase domain containing 2B
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434N062
Ensembl gene	ENSG00000144199
Ensembl biotype	protein_coding
Entrez	151313

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 22 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000272610, ENST00000414820, ENST00000463096, ENST00000468548, ENST00000474849, ENST00000483657, ENST00000850641, ENST00000902381, ENST00000902382, ENST00000902383, ENST00000902384, ENST00000902385, ENST00000902386, ENST00000902387, ENST00000940229, ENST00000940230, ENST00000940231, ENST00000940232, ENST00000940233, ENST00000940234, ENST00000940235, ENST00000954026, ENST00000954027, ENST00000954028, ENST00000954029, ENST00000954030

RefSeq mRNA: 3 — MANE Select: NM_001320848 NM_001320848, NM_001320849, NM_199336

CCDS: CCDS2030

Canonical transcript exons

ENST00000414820 — 9 exons

Exon	Start	End
ENSE00002443835	97086139	97086198
ENSE00002470216	97085699	97085861
ENSE00003300376	97083948	97084035
ENSE00003524857	97091462	97091712
ENSE00003582107	97090109	97090325
ENSE00003589319	97084169	97084277
ENSE00003900352	97083583	97083817
ENSE00004282427	97091863	97091988
ENSE00004282428	97094701	97094882

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.38.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	96.38	gold quality
left testis	UBERON:0004533	96.01	gold quality
right testis	UBERON:0004534	96.00	gold quality
cerebellar hemisphere	UBERON:0002245	95.90	gold quality
cerebellar cortex	UBERON:0002129	95.87	gold quality
cerebellum	UBERON:0002037	95.78	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.35	gold quality
right frontal lobe	UBERON:0002810	95.24	gold quality
testis	UBERON:0000473	95.16	gold quality
nucleus accumbens	UBERON:0001882	94.98	gold quality
substantia nigra	UBERON:0002038	94.98	gold quality
putamen	UBERON:0001874	94.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.77	gold quality
caudate nucleus	UBERON:0001873	94.56	gold quality
hypothalamus	UBERON:0001898	94.35	gold quality
primary visual cortex	UBERON:0002436	94.23	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.10	gold quality
Ammon’s horn	UBERON:0001954	94.09	gold quality
apex of heart	UBERON:0002098	94.06	gold quality
brain	UBERON:0000955	93.73	gold quality
amygdala	UBERON:0001876	93.71	gold quality
temporal lobe	UBERON:0001871	93.70	gold quality
cerebral cortex	UBERON:0000956	93.58	gold quality
left ovary	UBERON:0002119	93.57	gold quality
frontal cortex	UBERON:0001870	93.54	gold quality
anterior cingulate cortex	UBERON:0009835	93.54	gold quality
superior frontal gyrus	UBERON:0002661	93.37	gold quality
fundus of stomach	UBERON:0001160	93.35	gold quality
body of stomach	UBERON:0001161	92.99	gold quality
right ovary	UBERON:0002118	92.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting FAHD2B, 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-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-6749-5P	89.28	58.87	75
HSA-MIR-4523	85.64	61.16	64

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fahd2a	ENSDARG00000103759
drosophila_melanogaster	CG11251	FBGN0036346
drosophila_melanogaster	CG6028	FBGN0038924

Paralogs (3): FAH (ENSG00000103876), FAHD2A (ENSG00000115042), FAHD1 (ENSG00000180185)

Protein

Protein identifiers

Oxaloacetate tautomerase FAHD2B, mitochondrial — Q6P2I3 (reviewed: Q6P2I3)

Alternative names: Fumarylacetoacetate hydrolase domain-containing protein 2B

All UniProt accessions (1): Q6P2I3

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 (2): NP_001307777, NP_955368 (=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 (6 total): binding site 3, transit peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P2I3-F1	93.13	0.88

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: 28 (showing top): GOBP_OXALOACETATE_METABOLIC_PROCESS, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, chr2q11, GOMF_INTRAMOLECULAR_OXIDOREDUCTASE_ACTIVITY, GOMF_ISOMERASE_ACTIVITY, MIR144_3P, MIR4441, MIR4270, MIR3664_3P, MIR4530, MIR6754_5P, MIR4294, MIR510_5P

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

954 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAHD2B	FAM178B	Q8IXR5	696
FAHD2B	ANKRD36	A6QL64	624
FAHD2B	ANKRD39	Q53RE8	609
FAHD2B	ITPRIPL1	Q6GPH6	608
FAHD2B	CNNM3	Q8NE01	571
FAHD2B	ANKRD36C	Q5JPF3	512
FAHD2B	FER1L5	A0AVI2	512
FAHD2B	LMAN2L	Q9H0V9	478
FAHD2B	ANKRD36B	Q8N2N9	476
FAHD2B	ZNF514	Q96K75	474
FAHD2B	FAH	P16930	452
FAHD2B	ASTL	Q6HA08	447
FAHD2B	CDADC1	Q9BWV3	431
FAHD2B	ANKRD23	Q86SG2	425
FAHD2B	STARD7	Q9NQZ5	419
FAHD2B	VWA3B	Q502W6	419

IntAct

21 interactions, top by confidence:

A	B	Type	Score
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
FAHD2A	FAHD2B	psi-mi:“MI:0915”(physical association)	0.670
FAHD2A	DBT	psi-mi:“MI:0914”(association)	0.530
M		psi-mi:“MI:0914”(association)	0.350
FAHD2B	DBT	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
C1QTNF9B	DNASE2	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
LGALS9	CYB5A	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
SPANXN3	OGA	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): FAHD2B (Affinity Capture-MS), FAHD2B (Affinity Capture-MS), FAHD2B (Affinity Capture-MS), DBT (Affinity Capture-MS), FAHD2B (Affinity Capture-MS), FAHD2B (Affinity Capture-MS), BOLA3 (Affinity Capture-MS), GGT7 (Affinity Capture-MS), GBP1 (Affinity Capture-MS), DCAF6 (Affinity Capture-MS), CHMP2A (Affinity Capture-MS), FECH (Affinity Capture-MS), FAHD2A (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), EIF1AX (Affinity Capture-MS)

ESM2 similar proteins: A2XNR6, A3AJ77, B2RYW9, B9F3B6, F1MLX0, I6Y276, O04866, O49485, O86042, P21872, P34673, P51650, P52424, P53889, P76004, Q0QFQ3, Q10B63, Q10LR9, Q13VU0, Q1NEI7, Q2HJ98, Q2KIB0, Q2QWK9, Q3TC72, Q42942, Q46978, Q59A32, Q5RCX5, Q5RDW0, Q64737, Q6A2H2, Q6AYQ8, Q6GLT8, Q6P2I3, Q6P587, Q706S1, Q75LJ3, Q86I22, Q8BWF0, Q8R0F8

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1196 predictions. Top by Δscore:

Variant	Effect	Δscore
2:97084162:CACT:C	donor_loss	1.0000
2:97084163:ACT:A	donor_loss	1.0000
2:97084164:CTC:C	donor_loss	1.0000
2:97084165:TCA:T	donor_loss	1.0000
2:97084166:CA:C	donor_loss	1.0000
2:97084167:A:AC	donor_gain	1.0000
2:97084167:A:C	donor_loss	1.0000
2:97084168:C:A	donor_loss	1.0000
2:97084168:C:CT	donor_gain	1.0000
2:97084168:CT:C	donor_gain	1.0000
2:97084273:TGGAT:T	acceptor_gain	1.0000
2:97084274:GGAT:G	acceptor_gain	1.0000
2:97084275:GAT:G	acceptor_gain	1.0000
2:97084275:GATC:G	acceptor_loss	1.0000
2:97084276:AT:A	acceptor_gain	1.0000
2:97084277:TCTGA:T	acceptor_loss	1.0000
2:97084278:C:CC	acceptor_gain	1.0000
2:97084279:T:C	acceptor_loss	1.0000
2:97084283:A:AC	acceptor_gain	1.0000
2:97084283:A:C	acceptor_gain	1.0000
2:97084286:C:CT	acceptor_gain	1.0000
2:97085694:CCTA:C	donor_loss	1.0000
2:97085695:CTAC:C	donor_loss	1.0000
2:97085698:C:A	donor_loss	1.0000
2:97085698:CCTG:C	donor_gain	1.0000
2:97084031:CAAAC:C	acceptor_gain	0.9900
2:97084033:AACC:A	acceptor_loss	0.9900
2:97084037:T:A	acceptor_loss	0.9900
2:97084155:C:A	donor_gain	0.9900
2:97084160:GTCAC:G	donor_loss	0.9900

AlphaMissense

2050 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:97085829:G:C	F185L	0.979
2:97085829:G:T	F185L	0.979
2:97085831:A:G	F185L	0.979
2:97085742:G:C	F214L	0.977
2:97085742:G:T	F214L	0.977
2:97085744:A:G	F214L	0.977
2:97085830:A:G	F185S	0.977
2:97090172:G:C	F133L	0.974
2:97090172:G:T	F133L	0.974
2:97090174:A:G	F133L	0.974
2:97091611:G:C	F32L	0.974
2:97091611:G:T	F32L	0.974
2:97091613:A:G	F32L	0.974
2:97084201:G:C	F254L	0.970
2:97084201:G:T	F254L	0.970
2:97084203:A:G	F254L	0.970
2:97085808:A:C	S192R	0.967
2:97085808:A:T	S192R	0.967
2:97085810:T:G	S192R	0.967
2:97085758:T:A	K209I	0.962
2:97084252:G:C	C237W	0.957
2:97086189:A:G	W158R	0.955
2:97086189:A:T	W158R	0.955
2:97090229:A:C	N114K	0.955
2:97090229:A:T	N114K	0.955
2:97091612:A:G	F32S	0.952
2:97086167:A:T	V165D	0.950
2:97084009:A:T	V274D	0.949
2:97085821:G:T	A188D	0.948
2:97083952:A:T	L293H	0.945

dbSNP variants (sampled 300 via entrez): RS1000490957 (2:97086602 T>C), RS1000587371 (2:97081672 C>T), RS1001434365 (2:97093279 G>A), RS1001984675 (2:97081093 G>A), RS1002035279 (2:97081228 G>A,C), RS1002440312 (2:97094958 G>A), RS1002469278 (2:97088045 T>G), RS1002569371 (2:97091878 A>G), RS1003143471 (2:97084871 C>A), RS1003576555 (2:97093570 G>A), RS1003660610 (2:97079369 A>G), RS1003711537 (2:97079789 C>T), RS1003740463 (2:97086323 T>C), RS1003940064 (2:97090791 T>C), RS1004009526 (2:97086182 A>G,T)

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

7 associations (top):

Study	Trait	p-value
GCST010697_1	Cortical surface area (min-P)	6.000000e-12
GCST010698_17	Subcortical volume (min-P)	9.000000e-09
GCST010699_105	Brain morphology (min-P)	2.000000e-11
GCST010700_9	Cortical thickness (MOSTest)	9.000000e-14
GCST010701_54	Cortical surface area (MOSTest)	2.000000e-16
GCST010702_79	Subcortical volume (MOSTest)	5.000000e-09
GCST010703_322	Brain morphology (MOSTest)	1.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
Cadmium Chloride	decreases expression	2
TAK-243	increases sumoylation	1
sodium arsenate	decreases expression	1
ICG 001	increases expression	1
jinfukang	increases expression	1
Diazinon	increases methylation	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Zinc	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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