BAAT

Summary

BAAT (bile acid-CoA:amino acid N-acyltransferase, HGNC:932) is a protein-coding gene on chromosome 9q31.1, encoding Bile acid-CoA:amino acid N-acyltransferase (Q14032). Catalyzes the amidation of bile acids (BAs) with the amino acids taurine and glycine.

The protein encoded by this gene is a liver enzyme that catalyzes the transfer of C24 bile acids from the acyl-CoA thioester to either glycine or taurine, the second step in the formation of bile acid-amino acid conjugates. The bile acid conjugates then act as a detergent in the gastrointestinal tract, which enhances lipid and fat-soluble vitamin absorption. Defects in this gene are a cause of familial hypercholanemia (FHCA). Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 570 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypercholanemia, familial 1 (Strong, GenCC) — +3 more curated relationships
• Clinical variants (ClinVar): 212 total — 5 pathogenic, 3 likely-pathogenic
• GTEx eGene: eQTL in 22 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 11
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.05 (unconstrained)
• MANE Select transcript: NM_001701

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:932
Approved symbol	BAAT
Name	bile acid-CoA:amino acid N-acyltransferase
Location	9q31.1
Locus type	gene with protein product
Status	Approved
Aliases	BAT, BACAT
Ensembl gene	ENSG00000136881
Ensembl biotype	protein_coding
OMIM	602938
Entrez	570

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 22 protein_coding, 20 nonsense_mediated_decay

MANE Select: ENST00000259407

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000259407, ENST00000395051, ENST00000674556, ENST00000674791, ENST00000674909, ENST00000904170, ENST00000904171, ENST00000904172, ENST00000904173, ENST00000904174, ENST00000904175, ENST00000904176, ENST00000904177, ENST00000904178, ENST00000904179, ENST00000904180, ENST00000904181, ENST00000904182, ENST00000996708, ENST00000996709, ENST00000996710, ENST00000996711, ENST00000996712, ENST00000996713, ENST00000996714, ENST00000996715, ENST00000996716, ENST00000996717, ENST00000996718, ENST00000996719, ENST00000996720, ENST00000996723, ENST00000996725, ENST00000996726, ENST00001021607, ENST00001021609, ENST00001106572, ENST00001106573, ENST00001106575, ENST00001117339, ENST00001117340, ENST00001140247

RefSeq mRNA: 3 — MANE Select: NM_001701 NM_001127610, NM_001374715, NM_001701

CCDS: CCDS6752

Canonical transcript exons

ENST00000259407 — 4 exons

Exon	Start	End
ENSE00000926593	101368120	101368322
ENSE00001022933	101360417	101363015
ENSE00001671567	101370939	101371463
ENSE00003902194	101384855	101385006

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 98.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9917 / max 338.6330, expressed in 31 samples.

Highest expression (Bgee): liver, lobe of liver, gall bladder, islet of Langerhans, quadriceps femoris.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BAAT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 22 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 23 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	8.7e-52	+0.72	9:101385202:C:G
Heart Atrial Appendage	eqtl	9.8e-15	-0.67	9:101363660:C:A
Brain Cortex	eqtl	2.4e-10	-0.83	9:101374392:C:CTTATTA
Brain Frontal Cortex BA9	eqtl	1.6e-09	+0.53	9:101358568:T:G
Brain Caudate basal ganglia	eqtl	5.3e-08	-0.57	9:101348836:C:G
Brain Nucleus accumbens basal ganglia	eqtl	9.7e-08	-0.69	9:101374392:C:CTTATTA
Brain Cerebellar Hemisphere	eqtl	1.5e-07	+0.60	9:101387660:A:T
Liver	sqtl	5.2e-07	-0.92	9:101341259:A:C
Brain Hippocampus	eqtl	5.6e-07	-0.51	9:101348836:C:G
Brain Anterior cingulate cortex BA24	eqtl	3.8e-06	-0.65	9:101348836:C:G
Brain Hypothalamus	eqtl	3.0e-05	-0.65	9:101371866:C:T
Cells Cultured fibroblasts	eqtl	1.5e-04	-0.36	9:101395833:TAGAGAAGAGG:T
Brain Cerebellum	eqtl	3.7e-04	+0.55	9:101393189:C:T
Adrenal Gland	eqtl	1.0e-02	-0.35	9:101338601:A:G
Nerve Tibial	eqtl	1.8e-02	-0.38	9:101287019:T:TCAA
Brain Spinal cord cervical c-1	eqtl	2.0e-02	-0.48	9:101361839:G:A
Brain Putamen basal ganglia	eqtl	2.1e-02	-0.46	9:101320815:A:C
Lung	eqtl	2.5e-02	-1.31	9:102192412:CAT:C
Esophagus Muscularis	eqtl	3.0e-02	+0.25	9:101001196:G:A
Colon Sigmoid	eqtl	3.1e-02	+0.38	9:101387660:A:T

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
101737	0.8300	21
101735	0.0855	14
101736	0.0491	12
101734	0.0272	11

Top tissues by expression

showing 100 of 123 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	98.11	gold quality
right lobe of liver	UBERON:0001114	97.89	gold quality
gall bladder	UBERON:0002110	89.49	gold quality
islet of Langerhans	UBERON:0000006	74.76	gold quality
quadriceps femoris	UBERON:0001377	73.05	gold quality
cerebellar vermis	UBERON:0004720	70.49	gold quality
superior frontal gyrus	UBERON:0002661	69.08	gold quality
primary visual cortex	UBERON:0002436	67.02	gold quality
gastrocnemius	UBERON:0001388	66.47	gold quality
muscle of leg	UBERON:0001383	65.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.21	gold quality
skeletal muscle organ	UBERON:0014892	65.15	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	65.01	gold quality
pancreas	UBERON:0001264	64.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	64.34	gold quality
prefrontal cortex	UBERON:0000451	63.80	gold quality
frontal cortex	UBERON:0001870	63.62	gold quality
cerebral cortex	UBERON:0000956	62.98	gold quality
right frontal lobe	UBERON:0002810	62.74	gold quality
anterior cingulate cortex	UBERON:0009835	62.67	gold quality
cerebellum	UBERON:0002037	62.29	gold quality
cerebellar cortex	UBERON:0002129	62.28	gold quality
cerebellar hemisphere	UBERON:0002245	62.19	gold quality
cortical plate	UBERON:0005343	61.90	gold quality
putamen	UBERON:0001874	60.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	60.20	gold quality
nucleus accumbens	UBERON:0001882	59.98	gold quality
body of pancreas	UBERON:0001150	59.47	gold quality
brain	UBERON:0000955	59.43	gold quality
caudate nucleus	UBERON:0001873	59.08	gold quality
Ammon’s horn	UBERON:0001954	59.04	gold quality
hypothalamus	UBERON:0001898	58.78	gold quality
temporal lobe	UBERON:0001871	57.56	gold quality
amygdala	UBERON:0001876	57.54	gold quality
skeletal muscle tissue	UBERON:0001134	57.44	gold quality
thymus	UBERON:0002370	57.31	silver quality
colonic epithelium	UBERON:0000397	55.21	gold quality
substantia nigra	UBERON:0002038	53.70	gold quality
muscle tissue	UBERON:0002385	53.46	gold quality
calcaneal tendon	UBERON:0003701	52.01	gold quality
bone marrow cell	CL:0002092	51.57	gold quality
spinal cord	UBERON:0002240	50.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	50.64	gold quality
ganglionic eminence	UBERON:0004023	50.21	silver quality
adrenal tissue	UBERON:0018303	49.27	gold quality
right atrium auricular region	UBERON:0006631	47.99	gold quality
blood	UBERON:0000178	47.19	gold quality
lower esophagus mucosa	UBERON:0035834	46.38	silver quality
heart left ventricle	UBERON:0002084	46.34	gold quality
heart	UBERON:0000948	46.16	gold quality
material anatomical entity	UBERON:0000465	45.66	gold quality
multicellular organism	UBERON:0000468	45.66	gold quality
anatomical system	UBERON:0000467	45.51	gold quality
tonsil	UBERON:0002372	45.26	gold quality
kidney	UBERON:0002113	44.85	gold quality
left uterine tube	UBERON:0001303	44.24	gold quality
lung	UBERON:0002048	44.15	gold quality
bone marrow	UBERON:0002371	43.46	gold quality
myometrium	UBERON:0001296	43.08	gold quality
fundus of stomach	UBERON:0001160	43.00	silver quality
adrenal gland	UBERON:0002369	42.77	gold quality
endometrium	UBERON:0001295	42.71	gold quality
adenohypophysis	UBERON:0002196	42.67	silver quality
lymph node	UBERON:0000029	42.30	silver quality
granulocyte	CL:0000094	42.13	silver quality
left adrenal gland	UBERON:0001234	42.08	silver quality
small intestine Peyer’s patch	UBERON:0003454	42.01	gold quality
rectum	UBERON:0001052	41.97	silver quality
upper lobe of left lung	UBERON:0008952	41.95	gold quality
small intestine	UBERON:0002108	41.92	gold quality
adult mammalian kidney	UBERON:0000082	41.66	silver quality
right adrenal gland	UBERON:0001233	41.50	gold quality
sural nerve	UBERON:0015488	41.44	gold quality
lower esophagus muscularis layer	UBERON:0035833	41.37	gold quality
lower esophagus	UBERON:0013473	41.35	gold quality
descending thoracic aorta	UBERON:0002345	41.28	silver quality
mucosa of stomach	UBERON:0001199	41.17	silver quality
intestine	UBERON:0000160	41.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	41.01	silver quality
stomach	UBERON:0000945	40.64	gold quality
pituitary gland	UBERON:0000007	40.55	gold quality
ventricular zone	UBERON:0003053	40.50	silver quality
muscle layer of sigmoid colon	UBERON:0035805	40.47	silver quality
monocyte	CL:0000576	40.29	gold quality
metanephros cortex	UBERON:0010533	40.27	silver quality
colon	UBERON:0001155	40.22	silver quality
left adrenal gland cortex	UBERON:0035825	40.21	silver quality
spleen	UBERON:0002106	40.20	gold quality
body of stomach	UBERON:0001161	39.96	silver quality
body of uterus	UBERON:0009853	39.95	silver quality
right adrenal gland cortex	UBERON:0035827	39.88	silver quality
esophagus	UBERON:0001043	39.77	silver quality
vermiform appendix	UBERON:0001154	39.71	silver quality
transverse colon	UBERON:0001157	39.67	silver quality
mucosa of transverse colon	UBERON:0004991	39.64	silver quality
stromal cell of endometrium	CL:0002255	39.51	gold quality
ovary	UBERON:0000992	39.44	gold quality
left coronary artery	UBERON:0001626	39.30	silver quality
tibial nerve	UBERON:0001323	39.24	silver quality
ascending aorta	UBERON:0001496	39.07	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	53.64
E-ANND-3	no	2.62

HPA expression

RNA tissue specificity: Tissue enriched

22 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	674.5	medium
Gallbladder	tissue	16.4	medium
Postcentral gyrus	tissue	3.5
Hippocampus	tissue	2.0	not detected
Nucleus accumbens	tissue	1.6
Locus coeruleus	tissue	1.6
Choroid plexus	tissue	1.5
Bone marrow	tissue	1.2	not detected
Pancreas	tissue	0.9	not detected
Skeletal muscle	tissue	0.6	not detected
Tongue	tissue	0.6
Lung	tissue	0.4	not detected
Kidney	tissue	0.3	not detected
Retina	tissue	0.2
Heart muscle	tissue	0.1	not detected
Cerebral cortex	tissue	0.1	not detected
Adipose tissue	tissue	0.1	not detected
Epididymis	tissue	0.1	not detected
Frontal cortex	tissue	0.1
Small intestine	tissue	0.1	not detected
Somatosensory cortex	tissue	0.1
Occipital cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 182; highest nTPM — Somatosensory cortex, postcentral gyrus, ventral (white matter) (2.9), Precentral gyrus (2.8), Somatomor cortex, precentral gyrus (white matter) (2.8), Frontal eye field (2.7), Postcentral gyrus, middle (2.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A

miRNA regulators (miRDB)

Targeting BAAT by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 98 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-5010-3P	99.83	70.60	2357

Functional genomics

gnomAD constraint: pLI 0.000281, LOEUF 1.05, missense Z 0.648 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000259407 — one region, missense o/e 0.97.

Literature-anchored findings (GeneRIF, showing 9)

• there is an essential catalytic triad within hBAT consisting of Cys-235, His-362, and Asp-328 with Cys-235 serving as the probable nucleophile and thus the site of covalent attachment of the bile acid molecule (PMID:12239217)
• Familial hypercholanemia in Amish individuals is associated with mutations in tight junction protein 2 (encoded by TJP2, also known as ZO-2) and bile acid Coenzyme A: amino acid N-acyltransferase (encoded by BAAT). (PMID:12704386)
• cytosolic BACAT enzyme may play important roles in protection against toxicity by accumulation of unconjugated bile acids and non-esterified very long-chain fatty acids (PMID:12810727)
• hBAAT and rBaat are peroxisomal enzymes present in undetectable amounts in the cytosol. Unconjugated or deconjugated bile salts returning to the liver need to shuttle through the peroxisome before reentering the enterohepatic circulation. (PMID:17256745)
• identification of 3 novel SNPs, 147C>T in exon 2 (silent), 602G>C in exon 3 (Arg201Pro) & 1134C>T in exon 4 (silent), in the BAAT gene by resequencing the entire coding region and the exon-intron junctions of 100 Japanese individuals (PMID:17495420)
• Data show that dose-response inactivation by 4HNE (4-hydroxynonenal) of hBAT (human bile acid CoA:amino acid N-acyltransferase) and CKBB (cytosolic brain isoform of creatine kinase) is associated with site-specific modifications. (PMID:18793185)
• Case Report: mmunostaining may facilitate diagnosis in bile-acid amidation defects in bile acid-CoA: amino acid N-acyltransferase deficiency. (PMID:22783059)
• BAAT polymorphisms might not be associated with anti-tuberculosis drug-induced hepatotoxicity in the Chinese population (PMID:27155186)
• These results indicate that even small changes in the carboxy terminus of BAAT can have significant effects on activity and substrate specificity (PMID:27230263)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Baat	ENSMUSG00000039653
rattus_norvegicus	Baat	ENSRNOG00000007395
caenorhabditis_elegans	C31H5.6	WBGENE00007857
caenorhabditis_elegans		WBGENE00019404
caenorhabditis_elegans	T05E7.1	WBGENE00020258
caenorhabditis_elegans	W03D8.8	WBGENE00020989

Paralogs (4): ACOT2 (ENSG00000119673), ACOT4 (ENSG00000177465), ACOT1 (ENSG00000184227), ACOT6 (ENSG00000205669)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:106642) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating HDL cholesterol level	1
cataract	1
increased circulating triglyceride level	1
abnormal lymph node morphology	1
increased mean corpuscular volume	1
increased circulating alkaline phosphatase level	1
decreased circulating cholesterol level	1
improved glucose tolerance	1

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MRPL50	protein-coding	54534
ZNF189	protein-coding	7743
ALDOB	protein-coding	229

Protein

Protein identifiers

Bile acid-CoA:amino acid N-acyltransferase — Q14032 (reviewed: Q14032)

Alternative names: Bile acid-CoA thioesterase, Choloyl-CoA hydrolase, Glycine N-choloyltransferase, Long-chain fatty-acyl-CoA hydrolase

All UniProt accessions (3): A0A6Q8PF60, A0A6Q8PHR9, Q14032

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the amidation of bile acids (BAs) with the amino acids taurine and glycine. More than 95% of the BAs are N-acyl amidates with glycine and taurine. Amidation of BAs in the liver with glycine or taurine prior to their excretion into bile is an important biochemical event in bile acid metabolism. This conjugation (or amidation) plays several important biological roles in that it promotes the secretion of BAs and cholesterol into bile and increases the detergent properties of BAs in the intestine, which facilitates lipid and vitamin absorption. May also act as an acyl-CoA thioesterase that regulates intracellular levels of free fatty acids. In vitro, catalyzes the hydrolysis of long- and very long-chain saturated acyl-CoAs to the free fatty acid and coenzyme A (CoASH), and conjugates glycine to these acyl-CoAs.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol. Peroxisome.

Tissue specificity. Expressed in the gallbladder mucosa and pancreas. Expressed in hepatocytes (at protein level).

Disease relevance. Hypercholanemia, familial 3 (FHCA3) [MIM:619232] An autosomal recessive metabolic disorder characterized by reduced biliary secretion of conjugated bile acids, fat malabsorption, and fat-soluble vitamin deficiency. Clinical manifestations include rickets with variable growth failure due to vitamin D deficiency, and coagulopathy due to deficiency of vitamin K-dependent clotting factors. Additional variable features include pruritis, anemia, hepatomegaly, and bile duct proliferation on liver biopsy. Laboratory studies show abnormally increased levels of unconjugated bile acids. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the C/M/P thioester hydrolase family.

RefSeq proteins (3): NP_001121082, NP_001361644, NP_001692* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006862	Thio_Ohase/aa_AcTrfase	Domain
IPR014940	BAAT_C	Domain
IPR016662	Acyl-CoA_thioEstase_long-chain	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR042490	Thio_Ohase/BAAT_N	Homologous_superfamily

Pfam: PF04775, PF08840

Enzyme classification (BRENDA)

• EC 2.3.1.65 — bile acid-CoA:amino acid N-acyltransferase (BRENDA: 9 organisms, 82 substrates, 21 inhibitors, 34 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
TAURINE	0.6–6.7	11
GLYCINE	2.14–40	10
CHOLOYL-COA	0.0072–0.185	6
2-FLUORO-BETA-ALANINE	2	1
AMINOMETHANESULFONATE	0.8	1
AMINOMETHANESULFONIC ACID	2	1
BETA-ALANINE	175	1

Catalyzed reactions (Rhea)

• choloyl-CoA + glycine = glycocholate + CoA + H(+) (RHEA:14001)
• choloyl-CoA + H2O = cholate + CoA + H(+) (RHEA:14541)
• hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+) (RHEA:16645)
• dodecanoyl-CoA + H2O = dodecanoate + CoA + H(+) (RHEA:30135)
• octadecanoyl-CoA + H2O = octadecanoate + CoA + H(+) (RHEA:30139)
• chenodeoxycholoyl-CoA + H2O = chenodeoxycholate + CoA + H(+) (RHEA:31511)
• tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+) (RHEA:40119)
• eicosanoyl-CoA + H2O = eicosanoate + CoA + H(+) (RHEA:40147)
• docosanoyl-CoA + H2O = docosanoate + CoA + H(+) (RHEA:40783)
• tetracosanoyl-CoA + H2O = tetracosanoate + CoA + H(+) (RHEA:40787)
• hexacosanoyl-CoA + H2O = hexacosanoate + CoA + H(+) (RHEA:40791)
• choloyl-CoA + taurine = taurocholate + CoA + H(+) (RHEA:47100)

UniProt features (19 total): mutagenesis site 7, sequence variant 6, active site 3, modified residue 2, chain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14032-F1	95.31	0.92

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Hydrolases, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of ion transport and metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; cytosol

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

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

Catalytic / active sites (3)

Position	Role
235	charge relay system
328	charge relay system
362	charge relay system

Post-translational modifications (2)

Type	Positions
Phosphoserine	125, 416

Mutagenesis-validated functional residues (7)

Position	Phenotype
235	abolishes n-acyltransferase activity.
235	lowers n-acyltransferase activity; enhanced thioesterase activity presumably dependent on the formation of a bile acid-enzyme covalent …
328	abolishes n-acyltransferase activity.
362	abolishes n-acyltransferase activity.
372	retains n-acyltransferase activity.
417	translocation to peroxisomes.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 9; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

9 pathways:

ID	Pathway	Evidence
R-HSA-159418	Recycling of bile acids and salts	curated
R-HSA-193368	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol	curated
R-HSA-194068	Bile acid and bile salt metabolism	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-8957322	Metabolism of steroids	—
R-HSA-9033241	Peroxisomal protein import	electronic
R-HSA-9609507	Protein localization	—
R-HSA-192105	Synthesis of bile acids and bile salts	—

MSigDB gene sets: 238 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, MODULE_172, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_REGENERATION, MODULE_335, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, LEE_LIVER_CANCER_CIPROFIBRATE_DN, KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_BILE_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, CAGCAGG_MIR370

GO Biological Process (11): liver development (GO:0001889), bile acid conjugation (GO:0002152), glycine metabolic process (GO:0006544), fatty acid metabolic process (GO:0006631), acyl-CoA metabolic process (GO:0006637), bile acid biosynthetic process (GO:0006699), bile acid metabolic process (GO:0008206), taurine metabolic process (GO:0019530), animal organ regeneration (GO:0031100), lipid metabolic process (GO:0006629), monocarboxylic acid metabolic process (GO:0032787)

GO Molecular Function (12): acyltransferase activity (GO:0016746), choloyl-CoA hydrolase activity (GO:0033882), fatty acyl-CoA hydrolase activity (GO:0047617), glycine N-choloyltransferase activity (GO:0047963), carboxylic ester hydrolase activity (GO:0052689), medium-chain fatty acyl-CoA hydrolase activity (GO:0052815), long-chain fatty acyl-CoA hydrolase activity (GO:0052816), very long-chain fatty acyl-CoA hydrolase activity (GO:0052817), protein binding (GO:0005515), transferase activity (GO:0016740), hydrolase activity (GO:0016787), thiolester hydrolase activity (GO:0016790)

GO Cellular Component (3): peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), cytosol (GO:0005829)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Bile acid and bile salt metabolism	2
Synthesis of bile acids and bile salts	1
Protein localization	1
Metabolism of steroids	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

28 GO namespaces:

Category	Terms
fatty acyl-CoA hydrolase activity	3
bile acid metabolic process	2
monocarboxylic acid metabolic process	2
acyl-CoA hydrolase activity	2
hydrolase activity, acting on ester bonds	2
catalytic activity	2
gland development	1
hepaticobiliary system development	1
proteinogenic amino acid metabolic process	1
lipid metabolic process	1
nucleoside phosphate metabolic process	1
sulfur compound metabolic process	1
purine-containing compound metabolic process	1
monocarboxylic acid biosynthetic process	1
steroid metabolic process	1
alkanesulfonate metabolic process	1
regeneration	1
animal organ development	1
primary metabolic process	1
carboxylic acid metabolic process	1
transferase activity	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
binding	1
microbody	1
peroxisome	1
microbody lumen	1
cytoplasm	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
acyl-CoA metabolic process	BP	direct assay
bile acid biosynthetic process	BP	direct assay
bile acid conjugation	BP	direct assay
glycine metabolic process	BP	direct assay
taurine metabolic process	BP	direct assay
cytosol	CC	direct assay
peroxisome	CC	direct assay
glycine N-choloyltransferase activity	MF	direct assay
long-chain fatty acyl-CoA hydrolase activity	MF	direct assay
medium-chain fatty acyl-CoA hydrolase activity	MF	direct assay
very long-chain fatty acyl-CoA hydrolase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 662 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BAAT	GLYAT	Q6IB77	890
BAAT	SLC27A5	Q9Y2P5	840
BAAT	TJP2	Q9UDY2	835
BAAT	TMOD1	P28289	822
BAAT	ALDOB	P05062	777
BAAT	CYP8B1	Q9UNU6	716
BAAT	CYP7A1	P22680	680
BAAT	ABCB11	O95342	670
BAAT	CYP27A1	Q02318	661
BAAT	XPA	P23025	661
BAAT	TMC1	Q8TDI8	660
BAAT	CYP7B1	O75881	624
BAAT	ENTREP1	Q15884	618
BAAT	EPHX1	P07099	613
BAAT	HSD3B7	Q9H2F3	613

IntAct

Human interaction partners of BAAT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 37 partners by confidence:

Partner	Interaction type	MIscore	Records
CASP6	physical association	0.560	3
GOLGA8DP	physical association	0.560	3
GOLGA8F	physical association	0.560	3
HIP1	physical association	0.560	3
HMOX2	physical association	0.560	3
KAT5	physical association	0.560	3
LAMP2	physical association	0.560	3
LMO3	physical association	0.560	3
PPIA	physical association	0.560	3
PRPF40A	physical association	0.560	3
RAN	physical association	0.560	3
SETDB1	physical association	0.560	3
SH3GLB1	physical association	0.560	3
YWHAG	physical association	0.560	3
BMP2K	physical association	0.490	2
STAU1	physical association	0.400	2
APC	physical association	0.370	1
AURKA	physical association	0.370	1
BCL10	physical association	0.370	1
BUB1	physical association	0.370	1
CDKN2A	physical association	0.370	1
CTNNA1	physical association	0.370	1
DLC1	physical association	0.370	1
ERBB2	physical association	0.370	1
FBP1	physical association	0.370	1
FHL3	physical association	0.370	1
MCC	physical association	0.370	1
MLH1	physical association	0.370	1
MLH3	physical association	0.370	1
MUTYH	physical association	0.370	1

BioGRID (32 interactions; top human partners by supporting records): PEX5 (FRET; 2 records), STAU1 (Affinity Capture-MS; 2 records), APC (Two-hybrid), AURKA (Two-hybrid), BCL10 (Two-hybrid), BUB1 (Two-hybrid), CDKN2A (Two-hybrid), CTNNA1 (Two-hybrid), DDO (FRET), DHRS4 (FRET), DLC1 (Two-hybrid), ERBB2 (Two-hybrid), GOLGA8DP (Two-hybrid), GOLGA8EP (Two-hybrid), GOLGA8F (Two-hybrid)

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transcriptional Regulation by TP53	6	13.8×	1e-03
Cell Cycle	7	9.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of cell growth	5	21.2×	2e-03

Disease & clinical

Genetic variants

Variant evidence for BAAT: 212 ClinVar records (8 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	3
Uncertain significance	132
Likely benign	29
Benign	23

Top pathogenic / likely-pathogenic (8)

Showing all 8 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4903943	NM_001701.4(BAAT):c.388dup (p.Arg130fs)	Likely pathogenic	criteria provided, single submitter	1
4903944	NM_001701.4(BAAT):c.324T>G (p.Tyr108Ter)	Likely pathogenic	criteria provided, single submitter	1
6720	NM_001701.4(BAAT):c.226A>G (p.Met76Val)	Pathogenic	no assertion criteria provided	1
1048532	NM_001701.4(BAAT):c.1156G>A (p.Gly386Arg)	Pathogenic	no assertion criteria provided	1
1048533	NM_001701.4(BAAT):c.206A>T (p.Asp69Val)	Pathogenic	no assertion criteria provided	1
1048534	NM_001701.4(BAAT):c.58C>T (p.Arg20Ter)	Pathogenic	no assertion criteria provided	1
1048535	NM_001701.4(BAAT):c.250C>A (p.Pro84Thr)	Pathogenic	no assertion criteria provided	1
3347294	NM_001701.4(BAAT):c.584del (p.Asn195fs)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore BAAT’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 273):

Position(s)	Effect	Δscore	Sites
9:101368118–101368119	donor_loss	1.0000	5
9:101384854	donor_loss	1.0000
9:101368323–101368324	acceptor_loss	0.9900	6
9:101370938	donor_loss	0.9900
9:101384853–101384854	donor_loss	0.9900	3
9:101360560	acceptor_gain	0.9800
9:101363016–101363017	acceptor_loss	0.9800	6
9:101370937–101370938	donor_loss	0.9800	3
9:101371467	acceptor_gain	0.9800
9:101384854	donor_loss	0.9800

AlphaMissense

426 missense substitutions predicted likely pathogenic (of 2,712 scored), across 158 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D328	8	0.782	0.893
D165	8	0.738	0.815
F152	7	0.885	0.937
W399	7	0.870	0.959
F405	7	0.832	0.963
F44	7	0.805	0.958
H362	7	0.785	0.901
F211	6	0.816	0.943
Q395	6	0.796	0.916
F186	5	0.888	0.939
R130	5	0.868	0.946
S179	5	0.848	0.954
N258	5	0.845	0.949
F322	5	0.826	0.876
K93	5	0.770	0.882
G259	5	0.748	0.808
G361	5	0.737	0.841
G385	5	0.726	0.783
M244	5	0.717	0.825
D14	5	0.680	0.771

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	favorable	0.000467

Disease associations

OMIM: gene MIM:602938 | disease phenotypes: MIM:619232

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
bile acid conjugation defect 1	Strong	Autosomal recessive	2
hypercholanemia, familial 1	Strong	Autosomal recessive
familial hypercholanemia	Supportive	Autosomal recessive	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
bile acid CoA:amino acid N-acyltransferase deficiency	Moderate	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 8 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
Cholestasis	green
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Neonatal cholestasis	green
Paediatric disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (3): bile acid conjugation defect 1 (MONDO:0030991), hypercholanemia, familial 1 (MONDO:0031446), (MONDO:0011905)

HPO phenotypes

11 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000952	Jaundice
HP:0001399	Hepatic failure
HP:0002240	Hepatomegaly
HP:0002748	Rickets
HP:0002908	Conjugated hyperbilirubinemia
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0011463	Childhood onset
HP:0031956	Elevated circulating aspartate aminotransferase concentration
HP:0031964	Elevated circulating alanine aminotransferase concentration

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C564336	Hypercholanemia, Familial *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, affects cotreatment	5
Acetaminophen	decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression	2
Chenodeoxycholic Acid	decreases expression, affects cotreatment	2
Estradiol	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
senecionine	decreases expression	1
potassium bromate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentanal	decreases expression	1
nefazodone	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
ormosil	affects binding, decreases expression	1
jinfukang	decreases expression, affects cotreatment	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Atazanavir Sulfate	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Cholic Acids	affects cotreatment, affects expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.