DDTL

Summary

DDTL (D-dopachrome tautomerase like, HGNC:33446) is a protein-coding gene on chromosome 22q11.23, encoding Putative D-dopachrome decarboxylase-like protein (A6NHG4). May have a carboxy-lyase activity.

Predicted to enable phenylpyruvate tautomerase activity. Located in extracellular exosome.

Source: NCBI Gene 100037417 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 7 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001084393

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33446
Approved symbol	DDTL
Name	D-dopachrome tautomerase like
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000099974
Ensembl biotype	protein_coding
Entrez	100037417

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000215770, ENST00000897122

RefSeq mRNA: 1 — MANE Select: NM_001084393 NM_001084393

CCDS: CCDS42988

Canonical transcript exons

ENST00000215770 — 3 exons

Exon	Start	End
ENSE00001493396	23971286	23972556
ENSE00001661823	23966888	23967022
ENSE00001678640	23967386	23967561

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6200 / max 100.4801, expressed in 1807 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
209420	12.6200	1807

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	93.20	gold quality
liver	UBERON:0002107	89.03	gold quality
mucosa of transverse colon	UBERON:0004991	85.97	gold quality
body of pancreas	UBERON:0001150	85.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.64	gold quality
lower esophagus mucosa	UBERON:0035834	83.77	gold quality
apex of heart	UBERON:0002098	83.42	gold quality
metanephros cortex	UBERON:0010533	82.59	gold quality
cortex of kidney	UBERON:0001225	81.90	gold quality
fundus of stomach	UBERON:0001160	81.43	gold quality
body of stomach	UBERON:0001161	81.11	gold quality
adult mammalian kidney	UBERON:0000082	80.24	gold quality
transverse colon	UBERON:0001157	80.06	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.55	gold quality
heart left ventricle	UBERON:0002084	78.98	gold quality
stomach	UBERON:0000945	78.89	gold quality
small intestine	UBERON:0002108	78.86	gold quality
rectum	UBERON:0001052	78.75	gold quality
prostate gland	UBERON:0002367	78.63	gold quality
pancreas	UBERON:0001264	78.21	gold quality
kidney	UBERON:0002113	78.19	gold quality
spleen	UBERON:0002106	77.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.97	gold quality
blood	UBERON:0000178	77.84	gold quality
esophagus mucosa	UBERON:0002469	77.57	gold quality
intestine	UBERON:0000160	77.47	gold quality
endometrium	UBERON:0001295	77.47	gold quality
left ovary	UBERON:0002119	77.47	gold quality
colon	UBERON:0001155	77.27	gold quality
duodenum	UBERON:0002114	76.99	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	39.04
E-ANND-3	yes	9.23
E-CURD-112	yes	7.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting DDTL, 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-4500	99.99	72.72	2367
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-4266	98.53	67.29	1035

Literature-anchored findings (GeneRIF, showing 2)

• Authors performed genetic case-control CNV analyses to test for possible associations between schizophrenia and CNVs for the three genes GSTT1, DDTL, and GSTM1 in Japanese patients. (PMID:26175060)
• Genetic regulation of gene expression of MIF family members in lung tissue. (PMID:33046825)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddt	ENSDARG00000044751
mus_musculus	Ddt	ENSMUSG00000001666
rattus_norvegicus		ENSRNOG00000083406

Paralogs (2): DDT (ENSG00000099977), MIF (ENSG00000240972)

Protein

Protein identifiers

Putative D-dopachrome decarboxylase-like protein — A6NHG4 (reviewed: A6NHG4)

Alternative names: D-dopachrome tautomerase-like protein

All UniProt accessions (2): A6NHG4, A0A0F7RPW6

UniProt curated annotations — full annotation on UniProt →

Function. May have a carboxy-lyase activity.

Subcellular location. Cytoplasm.

Similarity. Belongs to the MIF family.

RefSeq proteins (1): NP_001077862* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001398	Macrophage_inhib_fac	Family
IPR014347	Tautomerase/MIF_sf	Homologous_superfamily
IPR019829	Macrophage_inhib_fac_CS	Conserved_site

Pfam: PF01187

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NHG4-F1	73.43	0.32

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 21 (showing top): GOMF_INTRAMOLECULAR_OXIDOREDUCTASE_ACTIVITY, GOMF_ISOMERASE_ACTIVITY, MIR4500, MIR548L, LET_7B_5P, LET_7A_5P_LET_7C_5P_LET_7E_5P, LET_7I_5P, LET_7F_5P, LET_7G_5P, MIR98_5P, MIR4534, MIR4678, MIR331_5P, DESCARTES_MAIN_FETAL_HEMATOPOIETIC_STEM_CELLS, DESCARTES_FETAL_KIDNEY_LYMPHOID_CELLS

GO Biological Process (0):

GO Molecular Function (2): lyase activity (GO:0016829), phenylpyruvate tautomerase activity (GO:0050178)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	1
intramolecular oxidoreductase activity, interconverting keto- and enol-groups	1
intracellular anatomical structure	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDTL	GSTT4	A0A1W2PR19	646
DDTL	GSTT2B	P0CG30	570
DDTL	LRRC75B	Q2VPJ9	542
DDTL	C22orf15	Q8WYQ4	507
DDTL	ATP5MGL	Q7Z4Y8	433
DDTL	RIMBP3B	A6NNM3	417
DDTL	DRICH1	Q6PGQ1	417
DDTL	SLC35E4	Q6ICL7	396
DDTL	GUCD1	Q96NT3	371
DDTL	CCNI2	Q6ZMN8	370
DDTL	TMEM121B	Q9BXQ6	350
DDTL	RIMBP3C	A6NJZ7	349
DDTL	H7C1H1	H7C1H1	348
DDTL	ZNF70	Q9UC06	348
DDTL	SLC2A11	Q9BYW1	337

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TRIM24	DDTL	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): TRIM24 (Affinity Capture-MS), ARHGDIA (Affinity Capture-MS), MTPN (Affinity Capture-MS), MDH1 (Affinity Capture-MS), TBCA (Affinity Capture-MS), CYCS (Affinity Capture-MS), CSTB (Affinity Capture-MS), RPS28 (Affinity Capture-MS), DDTL (Proximity Label-MS), DDTL (Proximity Label-MS), DDTL (Affinity Capture-MS), DDTL (Cross-Linking-MS (XL-MS)), DDTL (Proximity Label-MS), XPO1 (Co-fractionation), PPP2CA (Co-fractionation)

ESM2 similar proteins: A0A142I740, A2QM49, A5PK65, A6NHG4, A9SDL4, A9V2Y9, B2RXM4, B4G653, C5WU23, D3ZVR1, D4AWH0, D7PHZ1, F7D4X9, G0R6S7, K2RU68, O35215, O95755, O96347, P0DO34, P30046, P30111, P80254, P90835, P9WEP2, Q08CY5, Q0CS96, Q0DDI1, Q0IHU5, Q11177, Q18785, Q25313, Q28J83, Q4WQZ6, Q567W6, Q59750, Q5AXB0, Q5MFW3, Q5PQA5, Q5VVY1, Q5ZC83

Diamond homologs: A5PK65, A6NHG4, O35215, O55052, P14174, P30046, P80177, P80254, P80928, P81529, P91850, Q1ZZU7, Q28J83, Q4R549, Q5ZMG0, Q640C5, Q68FI3, Q6DN04, A9JSE7, P30904, P34884, Q02960, Q18785, O44786, P81748, Q76BK2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
253435	GRCh37/hg19 22q11.22-11.23(chr22:23258229-25046803)x3	Pathogenic
635766	GRCh37/hg19 22q11.22-11.23(chr22:22998284-25119103)x3	Likely pathogenic

SpliceAI

382 predictions. Top by Δscore:

Variant	Effect	Δscore
22:23967019:GGAC:G	donor_gain	1.0000
22:23967020:G:GT	donor_gain	1.0000
22:23967020:GAC:G	donor_gain	1.0000
22:23967023:G:GG	donor_gain	1.0000
22:23967018:CGGAC:C	donor_gain	0.9900
22:23967019:GGACG:G	donor_gain	0.9900
22:23967020:G:T	donor_gain	0.9900
22:23967020:GACG:G	donor_loss	0.9900
22:23967021:AC:A	donor_gain	0.9900
22:23967021:ACGTA:A	donor_loss	0.9900
22:23967022:CGTAA:C	donor_loss	0.9900
22:23967023:GTAA:G	donor_loss	0.9900
22:23967024:T:TG	donor_loss	0.9900
22:23967385:GC:G	acceptor_gain	0.9900
22:23967385:GCGC:G	acceptor_gain	0.9900
22:23967522:T:TG	donor_gain	0.9900
22:23967539:G:GT	donor_gain	0.9900
22:23967562:G:GG	donor_gain	0.9800
22:23967563:TGC:T	donor_loss	0.9800
22:23967564:GCG:G	donor_loss	0.9800
22:23967573:T:TA	donor_gain	0.9800
22:23967574:A:AA	donor_gain	0.9800
22:23967027:GC:G	donor_gain	0.9700
22:23967384:A:AG	acceptor_gain	0.9700
22:23967385:G:GG	acceptor_gain	0.9700
22:23967522:T:G	donor_gain	0.9700
22:23967557:G:GT	donor_gain	0.9700
22:23967566:G:C	donor_loss	0.9700
22:23967380:CCTCA:C	acceptor_loss	0.9600
22:23967381:CTCA:C	acceptor_loss	0.9600

AlphaMissense

856 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:23966941:T:A	N9K	0.968
22:23966941:T:G	N9K	0.968
22:23967013:A:C	K33N	0.955
22:23967013:A:T	K33N	0.955
22:23967387:G:C	R37P	0.950
22:23966921:T:C	F3L	0.949
22:23966923:C:A	F3L	0.949
22:23966923:C:G	F3L	0.949
22:23967396:T:A	V40E	0.944
22:23967462:T:A	I62N	0.941
22:23966994:C:A	A27D	0.940
22:23966919:C:A	P2Q	0.926
22:23967450:C:A	A58E	0.925
22:23967527:T:C	F84L	0.923
22:23967529:T:A	F84L	0.923
22:23967529:T:G	F84L	0.923
22:23966982:T:A	L23H	0.915
22:23966931:T:A	L6Q	0.914
22:23967011:A:G	K33E	0.914
22:23967390:T:A	V38E	0.910
22:23967405:G:C	R43P	0.904
22:23967462:T:G	I62S	0.903
22:23967521:T:C	F82L	0.902
22:23967523:T:A	F82L	0.902
22:23967523:T:G	F82L	0.902
22:23967012:A:T	K33I	0.899
22:23967528:T:C	F84S	0.897
22:23967402:T:A	V42E	0.896
22:23967012:A:C	K33T	0.895
22:23967464:T:C	S63P	0.895

dbSNP variants (sampled 300 via entrez): RS1000155777 (22:23970640 G>A,T), RS1001108851 (22:23969037 C>T), RS1001147883 (22:23969290 T>C), RS1001149768 (22:23971758 C>T), RS1001776114 (22:23970676 G>A), RS1003354064 (22:23969724 C>G), RS1004285833 (22:23969544 G>A,C), RS1005087550 (22:23972396 C>A,T), RS1005371092 (22:23965475 C>T), RS1005553864 (22:23970415 G>A), RS1005915199 (22:23970280 T>C), RS1006036899 (22:23970489 TATGAATGTCA>T), RS1006771 (22:23971817 G>T), RS1008893621 (22:23972111 T>A,C), RS1008924555 (22:23972290 T>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

2 associations (top):

Study	Trait	p-value
GCST001277_19	Liver enzyme levels (gamma-glutamyl transferase)	2.000000e-09
GCST003483_1	S-phenylmercapturic acid levels in smokers	3.000000e-134

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0007651	urinary S-phenylmercapturic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Rosiglitazone	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Smoke	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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