AFMID

Summary

AFMID (arylformamidase, HGNC:20910) is a protein-coding gene on chromosome 17q25.3, encoding Kynurenine formamidase (Q63HM1). Catalyzes the hydrolysis of N-formyl-L-kynurenine to L-kynurenine, the second step in the kynurenine pathway of tryptophan degradation.

Predicted to enable arylformamidase activity. Predicted to be involved in L-tryptophan catabolic process to kynurenine. Predicted to be located in cytosol and nucleus. Predicted to be active in cytoplasm.

Source: NCBI Gene 125061 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_001010982

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20910
Approved symbol	AFMID
Name	arylformamidase
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686F03259, KF
Ensembl gene	ENSG00000183077
Ensembl biotype	protein_coding
OMIM	621151
Entrez	125061

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 33 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000327898, ENST00000409257, ENST00000585419, ENST00000586542, ENST00000586731, ENST00000587750, ENST00000588199, ENST00000588800, ENST00000589107, ENST00000589256, ENST00000589664, ENST00000591256, ENST00000591538, ENST00000591952, ENST00000592988, ENST00000857463, ENST00000857464, ENST00000857465, ENST00000857466, ENST00000857467, ENST00000857468, ENST00000857469, ENST00000857470, ENST00000857471, ENST00000857472, ENST00000857473, ENST00000857474, ENST00000857475, ENST00000857476, ENST00000857477, ENST00000857478, ENST00000857479, ENST00000857480, ENST00000857481, ENST00000857482, ENST00000857483, ENST00000857484, ENST00000857485, ENST00000912342, ENST00000965675

RefSeq mRNA: 11 — MANE Select: NM_001010982 NM_001010982, NM_001145526, NM_001391999, NM_001392000, NM_001392001, NM_001392002, NM_001392003, NM_001392004, NM_001392005, NM_001392006, NM_001392007

CCDS: CCDS32750, CCDS45801

Canonical transcript exons

ENST00000409257 — 11 exons

Exon	Start	End
ENSE00001308714	78205093	78205190
ENSE00003481853	78205603	78205738
ENSE00003534056	78190970	78191060
ENSE00003551118	78202703	78202751
ENSE00003563869	78205440	78205518
ENSE00003608456	78204656	78204741
ENSE00003617529	78204828	78204900
ENSE00003628037	78202499	78202603
ENSE00003660990	78205946	78206050
ENSE00003668375	78187362	78187433
ENSE00003923340	78206911	78207702

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.1466 / max 419.0843, expressed in 1807 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163042	36.6022	1807
163041	0.5444	291

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.65	gold quality
metanephros cortex	UBERON:0010533	98.62	gold quality
body of pancreas	UBERON:0001150	97.12	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.88	gold quality
cerebellar hemisphere	UBERON:0002245	95.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.82	gold quality
right uterine tube	UBERON:0001302	95.77	gold quality
cerebellar cortex	UBERON:0002129	95.74	gold quality
right lung	UBERON:0002167	93.63	gold quality
cerebellum	UBERON:0002037	93.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.48	gold quality
skin of abdomen	UBERON:0001416	93.38	gold quality
right ovary	UBERON:0002118	93.18	gold quality
spinal cord	UBERON:0002240	93.12	gold quality
left ovary	UBERON:0002119	93.01	gold quality
minor salivary gland	UBERON:0001830	92.83	gold quality
right frontal lobe	UBERON:0002810	92.50	gold quality
apex of heart	UBERON:0002098	92.43	gold quality
upper lobe of left lung	UBERON:0008952	92.10	gold quality
gall bladder	UBERON:0002110	91.94	gold quality
skin of leg	UBERON:0001511	91.89	gold quality
prefrontal cortex	UBERON:0000451	91.76	gold quality
body of stomach	UBERON:0001161	91.75	gold quality
pancreas	UBERON:0001264	91.68	gold quality
adult mammalian kidney	UBERON:0000082	91.52	gold quality
rectum	UBERON:0001052	90.83	gold quality
right atrium auricular region	UBERON:0006631	90.65	gold quality
mucosa of transverse colon	UBERON:0004991	90.52	gold quality
anterior cingulate cortex	UBERON:0009835	90.29	gold quality
cortex of kidney	UBERON:0001225	90.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.16

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, ESR1

miRNA regulators (miRDB)

39 targeting AFMID, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051

Literature-anchored findings (GeneRIF, showing 1)

• A human-specific switch of alternatively spliced AFMID isoforms contributes to TP53 mutations and tumor recurrence in hepatocellular carcinoma (PMID:29449409)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	afmid	ENSDARG00000099106
mus_musculus	Afmid	ENSMUSG00000017718
rattus_norvegicus	Afmid	ENSRNOG00000050205
drosophila_melanogaster	KFase	FBGN0287695
caenorhabditis_elegans		WBGENE00017051

Paralogs (5): AADAC (ENSG00000114771), NCEH1 (ENSG00000144959), AADACL3 (ENSG00000188984), AADACL2 (ENSG00000197953), AADACL4 (ENSG00000204518)

Protein

Protein identifiers

Kynurenine formamidase — Q63HM1 (reviewed: Q63HM1)

Alternative names: Arylformamidase, N-formylkynurenine formamidase

All UniProt accessions (9): Q63HM1, K7EIX3, K7EK09, K7ELV9, K7EMI4, K7EMM5, K7EPF8, K7EQK5, W4VSQ7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of N-formyl-L-kynurenine to L-kynurenine, the second step in the kynurenine pathway of tryptophan degradation. Kynurenine may be further oxidized to nicotinic acid, NAD(H) and NADP(H). Required for elimination of toxic metabolites.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Domain organisation. The main chain amide nitrogen atoms of the second glycine and its adjacent residue in the HGGXW motif define the oxyanion hole, and stabilize the oxyanion that forms during the nucleophilic attack by the catalytic serine during substrate cleavage.

Pathway. Amino-acid degradation; L-tryptophan degradation via kynurenine pathway; L-kynurenine from L-tryptophan: step 2/2.

Similarity. Belongs to the kynurenine formamidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q63HM1-1	1	yes
Q63HM1-2	2

RefSeq proteins (11): NP_001010982, NP_001138998, NP_001378928, NP_001378929, NP_001378930, NP_001378931, NP_001378932, NP_001378933, NP_001378934, NP_001378935, NP_001378936 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013094	AB_hydrolase_3	Domain
IPR027519	KFase_ver/fungi-typ	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR050300	GDXG_lipolytic_enzyme	Family

Pfam: PF07859

Catalyzed reactions (Rhea), 1 shown:

• N-formyl-L-kynurenine + H2O = L-kynurenine + formate + H(+) (RHEA:13009)

UniProt features (7 total): active site 3, chain 1, short sequence motif 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q63HM1-F1	94.39	0.92

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): 164 (nucleophile); 247; 279

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-71240	Tryptophan catabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 118 (showing top): GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, REACTOME_TRYPTOPHAN_CATABOLISM, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_NADPLUS_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_INDOLE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOBP_BENZENE_CONTAINING_COMPOUND_METABOLIC_PROCESS, FISCHER_DREAM_TARGETS

GO Biological Process (3): obsolete L-tryptophan catabolic process to L-kynurenine (GO:0019441), ‘de novo’ NAD+ biosynthetic process from L-tryptophan (GO:0034354), L-tryptophan catabolic process (GO:0006569)

GO Molecular Function (3): arylformamidase activity (GO:0004061), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
aromatic amino acid metabolic process	1
NAD+ biosynthetic process	1
indole-containing compound metabolic process	1
L-amino acid metabolic process	1
proteinogenic amino acid metabolic process	1
aromatic amino acid catabolic process	1
indole-containing compound catabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AFMID	KMO	O15229	812
AFMID	TDO2	P48775	807
AFMID	KYNU	Q16719	788
AFMID	HAAO	P46952	787
AFMID	IDO2	Q6ZQW0	711
AFMID	QPRT	Q15274	707
AFMID	ACMSD	Q8TDX5	670
AFMID	KYAT1	Q16773	658
AFMID	KYAT3	Q6YP21	654
AFMID	IDO1	P14902	643
AFMID	AADAT	Q8N5Z0	543
AFMID	NAPRT	Q6XQN6	512
AFMID	ABHD17B	Q5VST6	497
AFMID	A0A494C066	A0A494C066	487
AFMID	ACOT4	Q8N9L9	481

IntAct

15 interactions, top by confidence:

A	B	Type	Score
AFMID	MEI4	psi-mi:“MI:0915”(physical association)	0.560
AFMID	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
AFMID	MED18	psi-mi:“MI:0915”(physical association)	0.560
MEI4	AFMID	psi-mi:“MI:0915”(physical association)	0.560
STC2	AFMID	psi-mi:“MI:0915”(physical association)	0.400
CFTR	AFMID	psi-mi:“MI:0915”(physical association)	0.370
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
AFMID	DDIT4L	psi-mi:“MI:0915”(physical association)	0.000
AFMID	MED18	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): AFMID (Affinity Capture-MS), AFMID (Affinity Capture-MS), AFMID (Co-fractionation), PCBD1 (Co-fractionation), AFMID (Affinity Capture-RNA), AFMID (Affinity Capture-MS), AFMID (Synthetic Lethality), AFMID (Two-hybrid), AFMID (Two-hybrid), MEI4 (Two-hybrid), AFMID (Affinity Capture-RNA), AFMID (Proximity Label-MS), AFMID (Affinity Capture-MS), AFMID (PCA), AFMID (Affinity Capture-RNA)

ESM2 similar proteins: A0A0S2E7V8, A0A0S2E7X0, A0A0S6XGG5, A0A286LEZ6, A0A3G1DJF0, A0A823A413, A3GGU3, A3LZU8, A5DNX8, A6ZRD1, A7TJ85, O14353, O94634, P0CI62, P0CS92, P0DPA8, P23060, P24521, P31688, P32643, P36591, P40389, P48445, P53178, P87241, P9WEK4, Q04066, Q07379, Q08282, Q09839, Q10170, Q4WVD1, Q59ZV4, Q5A013, Q5A931, Q5AV79, Q63HM1, Q6BKI8, Q6BT11, Q6C3P4

Diamond homologs: B5XB27, Q566U4, Q63HM1, Q6L5F5, Q8K4H1, Q94AS5, A0A0E4AET8, A0A0G3FWY4, I6Y9F7, P19835, P21837, P37967, P96402, Q01470, Q04456, Q1PET6, Q5VNW5, Q5XG92, Q5Z9I2, Q8VYP9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1382 predictions. Top by Δscore:

Variant	Effect	Δscore
17:78187431:GAG:G	donor_gain	1.0000
17:78187432:AGGTA:A	donor_loss	1.0000
17:78187434:G:GG	donor_gain	1.0000
17:78187434:G:T	donor_loss	1.0000
17:78191048:A:G	donor_gain	1.0000
17:78202491:T:A	acceptor_gain	1.0000
17:78202701:A:AG	acceptor_gain	1.0000
17:78202702:G:GG	acceptor_gain	1.0000
17:78202702:GCCTT:G	acceptor_gain	1.0000
17:78204654:A:AG	acceptor_gain	1.0000
17:78204655:G:GC	acceptor_gain	1.0000
17:78204655:GTAA:G	acceptor_gain	1.0000
17:78204901:G:GG	donor_gain	1.0000
17:78205519:G:GG	donor_gain	1.0000
17:78205601:A:AG	acceptor_gain	1.0000
17:78205601:AG:A	acceptor_gain	1.0000
17:78205602:G:GG	acceptor_gain	1.0000
17:78205602:GG:G	acceptor_gain	1.0000
17:78205602:GGGA:G	acceptor_gain	1.0000
17:78205726:G:GT	donor_gain	1.0000
17:78205734:ACCAG:A	donor_loss	1.0000
17:78205735:CCAG:C	donor_loss	1.0000
17:78205736:CAGGT:C	donor_loss	1.0000
17:78205737:AG:A	donor_loss	1.0000
17:78205738:GGTA:G	donor_loss	1.0000
17:78205739:GTACT:G	donor_loss	1.0000
17:78205740:T:A	donor_loss	1.0000
17:78191024:G:GT	donor_gain	0.9900
17:78191056:TGAAG:T	donor_loss	0.9900
17:78191057:GAAGG:G	donor_loss	0.9900

AlphaMissense

1979 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:78204863:A:C	S144R	0.980
17:78204865:C:A	S144R	0.980
17:78204865:C:G	S144R	0.980
17:78205454:A:C	S194R	0.972
17:78205456:T:A	S194R	0.972
17:78205456:T:G	S194R	0.972
17:78205622:A:C	S222R	0.961
17:78205624:C:A	S222R	0.961
17:78205624:C:G	S222R	0.961
17:78202738:T:A	W99R	0.957
17:78202738:T:C	W99R	0.957
17:78205115:T:C	S164P	0.956
17:78205709:T:C	F251L	0.955
17:78205711:C:A	F251L	0.955
17:78205711:C:G	F251L	0.955
17:78206003:T:C	F280L	0.952
17:78206005:T:A	F280L	0.952
17:78206005:T:G	F280L	0.952
17:78205716:G:C	R253P	0.946
17:78205455:G:T	S194I	0.945
17:78206002:C:A	H279Q	0.943
17:78206002:C:G	H279Q	0.943
17:78202720:T:C	F93L	0.938
17:78202722:C:A	F93L	0.938
17:78202722:C:G	F93L	0.938
17:78204672:T:C	F109L	0.935
17:78204674:C:A	F109L	0.935
17:78204674:C:G	F109L	0.935
17:78202740:G:C	W99C	0.934
17:78202740:G:T	W99C	0.934

dbSNP variants (sampled 300 via entrez): RS1000291354 (17:78205300 G>A), RS1000367993 (17:78186021 G>A), RS1000693784 (17:78190116 C>G,T), RS1000712127 (17:78196137 T>C,G), RS1000922269 (17:78190705 G>A), RS1001051145 (17:78201067 G>A), RS1001053959 (17:78201291 C>T), RS1001145270 (17:78190468 A>G), RS1001351504 (17:78185890 C>A,G,T), RS1001425163 (17:78185699 T>G), RS1001653414 (17:78200708 G>A), RS1001937456 (17:78201645 A>G), RS1002021249 (17:78195102 A>C,G), RS1002072153 (17:78195489 G>A), RS1002304873 (17:78189717 G>A,T)

Disease associations

OMIM: gene MIM:621151 | 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
GCST004785_35	Vitiligo	2.000000e-06
GCST009733_186	Urinary metabolite levels in chronic kidney disease	1.000000e-27
GCST009733_74	Urinary metabolite levels in chronic kidney disease	2.000000e-13
GCST010397_118	Gut microbiota (bacterial taxa, rank normal transformation method)	5.000000e-07
GCST012020_136	Serum metabolite levels	4.000000e-43
GCST012020_149	Serum metabolite levels	5.000000e-12
GCST012353_7	Serum metabolite concentrations in chronic kidney disease	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8071253	AFMID, TK1		0.00	0

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects binding, increases reaction, decreases expression (+1 more)	3
aristolochic acid I	increases expression	1
bisphenol A	affects expression	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
licochalcone B	increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Doxorubicin	decreases expression	1
Gallic Acid	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
N-Nitrosopyrrolidine	decreases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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