TXNL4A

Summary

TXNL4A (thioredoxin like 4A, HGNC:30551) is a protein-coding gene on chromosome 18q23, encoding Thioredoxin-like protein 4A (P83876). Plays a role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes that are involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

The protein encoded by this gene is a member of the U5 small ribonucleoprotein particle (snRNP), and is involved in pre-mRNA splicing. This protein contains a thioredoxin-like fold and it is expected to interact with multiple proteins. Protein-protein interactions have been observed with the polyglutamine tract-binding protein 1 (PQBP1). Mutations in both the coding region and promoter region of this gene have been associated with Burn-McKeown syndrome, which is a rare disorder characterized by craniofacial dysmorphisms, cardiac defects, hearing loss, and bilateral choanal atresia. A pseudogene of this gene is found on chromosome 2. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10907 — RefSeq curated summary.

At a glance

• Gene–disease (curated): choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome (Definitive, ClinGen)
• Clinical variants (ClinVar): 36 total — 7 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 38
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_006701

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30551
Approved symbol	TXNL4A
Name	thioredoxin like 4A
Location	18q23
Locus type	gene with protein product
Status	Approved
Aliases	U5-15kD, DIM1, HsT161, DIB1, SNRNP15
Ensembl gene	ENSG00000141759
Ensembl biotype	protein_coding
OMIM	611595
Entrez	10907

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000269601, ENST00000355491, ENST00000585474, ENST00000585769, ENST00000586295, ENST00000586612, ENST00000586825, ENST00000588162, ENST00000589926, ENST00000591711, ENST00000592837, ENST00000592957

RefSeq mRNA: 5 — MANE Select: NM_006701 NM_001303471, NM_001305557, NM_001305563, NM_001305564, NM_006701

CCDS: CCDS32852, CCDS82260

Canonical transcript exons

ENST00000269601 — 3 exons

Exon	Start	End
ENSE00002896999	79988240	79988563
ENSE00002973543	79970813	79973856
ENSE00003688045	79977598	79977701

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 98.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 120.9041 / max 731.6640, expressed in 1828 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172670	114.8730	1827
172669	3.0484	1426
172671	1.7376	884
172668	0.8921	580
172672	0.2999	130
172667	0.0532	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.81	gold quality
amygdala	UBERON:0001876	98.05	gold quality
right testis	UBERON:0004534	98.00	gold quality
left testis	UBERON:0004533	97.92	gold quality
endothelial cell	CL:0000115	97.88	gold quality
adenohypophysis	UBERON:0002196	97.88	gold quality
pituitary gland	UBERON:0000007	97.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.84	gold quality
prefrontal cortex	UBERON:0000451	97.80	gold quality
cervix squamous epithelium	UBERON:0006922	97.77	gold quality
gingival epithelium	UBERON:0001949	97.75	gold quality
right frontal lobe	UBERON:0002810	97.65	gold quality
substantia nigra	UBERON:0002038	97.63	gold quality
periodontal ligament	UBERON:0008266	97.62	gold quality
gingiva	UBERON:0001828	97.59	gold quality
nucleus accumbens	UBERON:0001882	97.57	gold quality
cingulate cortex	UBERON:0003027	97.57	gold quality
anterior cingulate cortex	UBERON:0009835	97.52	gold quality
putamen	UBERON:0001874	97.46	gold quality
mucosa of transverse colon	UBERON:0004991	97.44	gold quality
sperm	CL:0000019	97.37	gold quality
midbrain	UBERON:0001891	97.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.36	gold quality
body of pancreas	UBERON:0001150	97.34	gold quality
caudate nucleus	UBERON:0001873	97.32	gold quality
spinal cord	UBERON:0002240	97.25	gold quality
male germ cell	CL:0000015	97.22	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.20	gold quality
substantia nigra pars compacta	UBERON:0001965	97.16	gold quality
hypothalamus	UBERON:0001898	97.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting TXNL4A, 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-190A-3P	100.00	80.35	5520
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-3138	98.41	67.53	744
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-6841-3P	98.08	66.54	604
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-424-3P	97.20	65.86	385
HSA-MIR-215-3P	97.02	68.01	1209
HSA-MIR-5579-3P	97.00	68.81	1111
HSA-MIR-555	95.92	65.25	564
HSA-MIR-5704	94.82	67.46	448

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• human dim1 is a peptidase with autocleavage activity that results in a thioredoxin-like core (PMID:17177886)
• frameshift mutations in the PQBP-1 gene lead to expression of mutants lacking the ability to interact with U5-15kD (PMID:20307692)
• Reporter gene and in vivo assays showed that the promoter deletions led to reduced expression of TXNL4A. Depletion of TXNL4A (Dib1) in yeast demonstrated reduced assembly of the tri-snRNP complex. (PMID:25434003)
• results suggest that the interaction between PQBP1 and WBP11 negatively modulates the U5-15kD binding of PQBP1 by an allosteric mechanism (PMID:27314904)
• Recessive variants in TXNL4A were identified in two individuals with Burn-McKeown syndrome as well as in three individuals (from two families) with isolated choanal atresia. (PMID:28905882)
• The Renpenning syndrome-associated protein PQBP1 facilitates the nuclear import of splicing factor TXNL4A through the karyopherin beta2 receptor. (PMID:32041777)
• Burn-McKeown syndrome with biallelic promoter type 2 deletion in TXNL4A in two siblings. (PMID:32187816)
• Expanding the genotypic spectrum of TXNL4A variants in Burn-McKeown syndrome. (PMID:34713892)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	txnl4a	ENSDARG00000036190
mus_musculus	Txnl4a	ENSMUSG00000057130
drosophila_melanogaster	Dim1	FBGN0031601
caenorhabditis_elegans		WBGENE00235102

Paralogs (1): TXNL4B (ENSG00000140830)

Protein

Protein identifiers

Thioredoxin-like protein 4A — P83876 (reviewed: P83876)

Alternative names: DIM1 protein homolog, Spliceosomal U5 snRNP-specific 15 kDa protein, Thioredoxin-like U5 snRNP protein U5-15kD

All UniProt accessions (7): P83876, K7EJU2, K7EMX5, K7EPA6, K7ES07, K7ESL1, O14835

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes that are involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).

Subunit / interactions. Component of the precatalytic spliceosome (spliceosome B complex). Component of the U5 snRNP complex. Component of the U4/U6-U5 tri-snRNP complex. The U4/U6-U5 tri-snRNP complex is a building block of the precatalytic spliceosome (spliceosome B complex). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. Directly interacts with CD2BP2. Interacts with HNRPF, HNRPH2, NEDD9 and PQBP1. Interacts with ERBB4.

Subcellular location. Nucleus.

Post-translational modifications. The disulfide bond seen in structures determined by X-ray crystallography and NMR is not essential for protein folding and function.

Disease relevance. Burn-McKeown syndrome (BMKS) [MIM:608572] A disease characterized by choanal atresia, sensorineural deafness, cardiac defects, and typical craniofacial dysmorphism consisting of narrow palpebral fissures, coloboma of the lower eyelids, prominent nose with high nasal bridge, short philtrum, cleft lip and/or palate, and large and protruding ears. Intellectual development is normal. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the DIM1 family.

RefSeq proteins (5): NP_001290400, NP_001292486, NP_001292492, NP_001292493, NP_006692* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004123	Dim1	Family
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF02966

UniProt features (19 total): strand 8, turn 4, helix 3, chain 1, modified residue 1, disulfide bond 1, mutagenesis site 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1QGV	X-RAY DIFFRACTION	1.4
4BWQ	X-RAY DIFFRACTION	2.1
1SYX	X-RAY DIFFRACTION	2.35
4BWS	X-RAY DIFFRACTION	2.5
4CDO	X-RAY DIFFRACTION	2.5
8H6L	ELECTRON MICROSCOPY	2.6
8H6K	ELECTRON MICROSCOPY	2.7
6QW6	ELECTRON MICROSCOPY	2.92
8Q7N	ELECTRON MICROSCOPY	3.1
8QOZ	ELECTRON MICROSCOPY	3.1
8QPE	ELECTRON MICROSCOPY	3.1
8H6E	ELECTRON MICROSCOPY	3.2
8H6J	ELECTRON MICROSCOPY	3.25
6QX9	ELECTRON MICROSCOPY	3.28
8QP8	ELECTRON MICROSCOPY	3.5
8QPA	ELECTRON MICROSCOPY	3.7
8QPB	ELECTRON MICROSCOPY	3.7
6AHD	ELECTRON MICROSCOPY	3.8
8QP9	ELECTRON MICROSCOPY	4.1
8QZS	ELECTRON MICROSCOPY	4.1
8QPK	ELECTRON MICROSCOPY	4.2
8R09	ELECTRON MICROSCOPY	4.3
8R0B	ELECTRON MICROSCOPY	4.4
5O9Z	ELECTRON MICROSCOPY	4.5
8QO9	ELECTRON MICROSCOPY	5.29
6AH0	ELECTRON MICROSCOPY	5.7
8R0A	ELECTRON MICROSCOPY	5.8
8R08	ELECTRON MICROSCOPY	6.1
8RM5	ELECTRON MICROSCOPY	6.9
3JCR	ELECTRON MICROSCOPY	7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P83876-F1	88.21	0.71

Functional residue map

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

Post-translational modifications (1): 132

Disulfide bonds (1): 38–79

Mutagenesis-validated functional residues (1):

Position	Phenotype
38	viable when expressed in s.pombe.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 245 (showing top): MORF_DNMT1, MORF_RRM1, MORF_HDAC2, PUJANA_CHEK2_PCC_NETWORK, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, MORF_BUB3, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, MORF_PRKDC, REACTOME_MRNA_SPLICING, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, MORF_AP3D1, GOBP_SPLICEOSOMAL_SNRNP_ASSEMBLY, REACTOME_METABOLISM_OF_RNA

GO Biological Process (6): spliceosomal complex assembly (GO:0000245), RNA splicing, via transesterification reactions (GO:0000375), mRNA splicing, via spliceosome (GO:0000398), cell division (GO:0051301), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U5 snRNP (GO:0005682), cytosol (GO:0005829), U4/U6 x U5 tri-snRNP complex (GO:0046540), U2-type precatalytic spliceosome (GO:0071005), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	2
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
mRNA splicing, via spliceosome	1
protein-RNA complex assembly	1
RNA splicing	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
cellular process	1
mRNA metabolic process	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
spliceosomal snRNP complex	1
cytoplasm	1
U5 snRNP	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TXNL4A	PQBP1	O60828	858
TXNL4A	EFTUD2	Q15029	782
TXNL4A	DDX23	Q9BUQ8	735
TXNL4A	PRPF31	Q8WWY3	716
TXNL4A	TXN	P10599	689
TXNL4A	PLRG1	O43660	676
TXNL4A	NEDD9	Q14511	662
TXNL4A	CD2BP2	O95400	657
TXNL4A	HDAC6	Q9UBN7	649
TXNL4A	AURKA	O14965	635
TXNL4A	PRPF8	Q6P2Q9	619
TXNL4A	PRPF6	O94906	613
TXNL4A	SNRNP200	O75643	612
TXNL4A	AAR2	Q9Y312	569
TXNL4A	SLC66A2	Q8N2U9	566

IntAct

79 interactions, top by confidence:

A	B	Type	Score
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
CD2BP2	SNRNP200	psi-mi:“MI:0914”(association)	0.800
PRPF6	TXNL4A	psi-mi:“MI:0915”(physical association)	0.790
TXNL4A	PRPF6	psi-mi:“MI:0915”(physical association)	0.790
TXNL4A	CD2BP2	psi-mi:“MI:0915”(physical association)	0.790
TXNL4A	CD2BP2	psi-mi:“MI:0407”(direct interaction)	0.790
PRPF6	SART1	psi-mi:“MI:0914”(association)	0.750
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
PRPF8	PRPF4	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SNRNP40	PRPF4	psi-mi:“MI:0914”(association)	0.640
EXOC5	TXNL4A	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	TXNL4A	psi-mi:“MI:0915”(physical association)	0.560
TXNL4A	EXOC5	psi-mi:“MI:0915”(physical association)	0.560
TXNL4A	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
TXNL4A	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
RHEBL1	TXNL4A	psi-mi:“MI:0915”(physical association)	0.550
TXNL4A	RHEBL1	psi-mi:“MI:0915”(physical association)	0.550
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPF	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
EFTUD2	AQR	psi-mi:“MI:0914”(association)	0.530
SNRNP40	AQR	psi-mi:“MI:0914”(association)	0.530

BioGRID (121): TXNL4A (Two-hybrid), LZTS2 (Two-hybrid), TXNL4A (Affinity Capture-MS), TXNL4A (Affinity Capture-MS), TXNL4A (Affinity Capture-MS), RHEBL1 (Two-hybrid), TXNL4A (Affinity Capture-RNA), TXNL4A (Affinity Capture-MS), TXNL4A (Affinity Capture-MS), TXNL4A (Affinity Capture-MS), TXNL4A (Affinity Capture-MS), TXNL4A (Affinity Capture-MS), TXNL4A (Affinity Capture-MS), TXNL4A (Affinity Capture-MS), TXNL4A (Affinity Capture-MS)

ESM2 similar proteins: A1JJM7, A4TPU3, A7FM34, A7ZHK9, A9KQ75, A9MPN4, A9R1H5, B1JK46, B1LGS1, B2K4I1, B4JLX2, B4L535, B4M709, B7MBA3, B7MNY2, B7NI80, B7UIG8, O01258, O13711, O43865, P0A7F6, P21081, P33863, P83876, P83877, P87215, Q02331, Q06819, Q0T880, Q0TLL4, Q0W2C6, Q197B6, Q197B9, Q1C3U6, Q1CLX2, Q1RG71, Q21534, Q553S5, Q6DH23, Q6FMI2

Diamond homologs: P83876, P83877, P87215, Q06819, Q553S5, Q6FMI2, Q75BD8, Q8BUH1, Q9FE62, Q9NX01

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TXNL4A	“form complex”	“U4/U6.U5 snRNP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
Metabolism of non-coding RNA	6	61.4×	1e-08
mRNA Splicing - Minor Pathway	12	43.3×	4e-15
SARS-CoV-2 modulates host translation machinery	7	25.3×	3e-07
mRNA Splicing	14	24.8×	2e-14
snRNP Assembly	7	23.9×	4e-07
mRNA Splicing - Major Pathway	27	23.8×	1e-28
Processing of Capped Intron-Containing Pre-mRNA	15	19.9×	3e-14
mRNA Polyadenylation	13	18.4×	6e-12

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal tri-snRNP complex assembly	6	93.6×	1e-09
spliceosomal snRNP assembly	11	88.8×	3e-17
RNA splicing, via transesterification reactions	8	69.3×	2e-11
U2-type prespliceosome assembly	7	60.7×	1e-09
spliceosomal complex assembly	7	58.5×	1e-09
mRNA splicing, via spliceosome	28	35.6×	3e-34
RNA splicing	17	20.8×	4e-16
mRNA processing	9	9.8×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	9
Likely benign	2
Benign	9

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
162205	NC_000018.9:g.77748356G>A	Pathogenic
162206	NC_000018.9:g.77748262delA	Pathogenic
162207	NM_006701.4(TXNL4A):c.258_429del172 (p.Asn87Alafs)	Pathogenic
1699951	NM_006701.5(TXNL4A):c.93_94del (p.His32fs)	Pathogenic
1699952	NM_006701.5(TXNL4A):c.258-3C>G	Pathogenic
242601	NC_000018.9:g.76854774_78077248del1222475	Pathogenic
253189	NM_006701.2:c.Exon 3 deletion	Pathogenic
1679370	NM_006701.5(TXNL4A):c.288dup (p.Gly97fs)	Likely pathogenic
451615	NM_006701.5(TXNL4A):c.88_110del (p.Phe30fs)	Likely pathogenic

SpliceAI

748 predictions. Top by Δscore:

Variant	Effect	Δscore
18:79973852:TGTTC:T	acceptor_gain	1.0000
18:79973854:TTC:T	acceptor_gain	1.0000
18:79973855:TC:T	acceptor_gain	1.0000
18:79973856:CC:C	acceptor_gain	1.0000
18:79973857:C:CC	acceptor_gain	1.0000
18:79973857:CT:C	acceptor_loss	1.0000
18:79973858:T:A	acceptor_loss	1.0000
18:79977593:CGTA:C	donor_loss	1.0000
18:79977594:GTA:G	donor_loss	1.0000
18:79977595:TACC:T	donor_loss	1.0000
18:79977596:A:AG	donor_loss	1.0000
18:79977597:C:G	donor_loss	1.0000
18:79988236:CTACC:C	donor_loss	1.0000
18:79988237:TAC:T	donor_loss	1.0000
18:79973853:GTTC:G	acceptor_gain	0.9900
18:79973863:C:CT	acceptor_gain	0.9900
18:79973864:G:T	acceptor_gain	0.9900
18:79977591:AACGT:A	donor_loss	0.9900
18:79977592:ACGTA:A	donor_loss	0.9900
18:79977702:C:CG	acceptor_loss	0.9900
18:79986600:A:AC	donor_gain	0.9900
18:79986601:C:CC	donor_gain	0.9900
18:79988239:CCTT:C	donor_gain	0.9900
18:79988242:T:A	donor_gain	0.9900
18:79973860:C:CT	acceptor_gain	0.9800
18:79973861:A:T	acceptor_gain	0.9800
18:79977634:TCA:T	donor_gain	0.9700
18:79977640:A:C	donor_gain	0.9600
18:79977702:C:CC	acceptor_gain	0.9600
18:79986646:G:C	donor_gain	0.9400

AlphaMissense

964 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:79973711:C:G	D135H	1.000
18:79973725:A:T	V130E	1.000
18:79973728:A:G	L129P	1.000
18:79973732:C:G	G128R	1.000
18:79973734:C:G	R127P	1.000
18:79973737:C:T	G126D	1.000
18:79973738:C:G	G126R	1.000
18:79973746:G:T	A123D	1.000
18:79973749:C:T	G122E	1.000
18:79973750:C:A	G122W	1.000
18:79973750:C:G	G122R	1.000
18:79973750:C:T	G122R	1.000
18:79973804:A:G	W104R	1.000
18:79973804:A:T	W104R	1.000
18:79973811:C:A	K101N	1.000
18:79973811:C:G	K101N	1.000
18:79973813:T:C	K101E	1.000
18:79973814:G:C	N100K	1.000
18:79973814:G:T	N100K	1.000
18:79973817:G:C	N99K	1.000
18:79973817:G:T	N99K	1.000
18:79973820:G:C	N98K	1.000
18:79973820:G:T	N98K	1.000
18:79973824:C:A	G97V	1.000
18:79973824:C:T	G97D	1.000
18:79973825:C:A	G97C	1.000
18:79973825:C:G	G97R	1.000
18:79973830:C:A	G95V	1.000
18:79973830:C:T	G95E	1.000
18:79973831:C:A	G95W	1.000

dbSNP variants (sampled 300 via entrez): RS1000046475 (18:80003386 C>T), RS1000168287 (18:79988446 G>A), RS1000192630 (18:80023054 T>C), RS1000268736 (18:79979916 T>C,G), RS1000333093 (18:79985325 G>A,T), RS1000345378 (18:80025874 C>T), RS1000411728 (18:80032151 C>T), RS1000420438 (18:80025595 C>T), RS1000483261 (18:79990566 T>C), RS1000490038 (18:80031326 G>A), RS1000548025 (18:79972915 A>G,T), RS1000599797 (18:79978659 A>C,G), RS1000691872 (18:80020107 G>A,C), RS1000744655 (18:80030735 G>A), RS1000744853 (18:80024241 G>A)

Disease associations

OMIM: gene MIM:611595 | disease phenotypes: MIM:608572

GenCC curated gene-disease

Disease	Classification	Inheritance
choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome	Definitive	AR

Mondo (1): choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome (MONDO:0012064)

Orphanet (1): Burn-McKeown syndrome (Orphanet:1200)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000089	Renal hypoplasia
HP:0000122	Unilateral renal agenesis
HP:0000160	Narrow mouth
HP:0000174	Abnormal palate morphology
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000204	Cleft upper lip
HP:0000233	Thin vermilion border
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000338	Hypomimic face
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000384	Preauricular skin tag
HP:0000405	Conductive hearing impairment
HP:0000411	Protruding ear
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000453	Choanal atresia
HP:0000478	Abnormality of the eye
HP:0000504	Abnormality of vision
HP:0000581	Blepharophimosis
HP:0000652	Lower eyelid coloboma
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001671	Abnormal cardiac septum morphology

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563682	Oculootofacial Dysplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases expression	3
Valproic Acid	affects expression, increases expression	2
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
ICG 001	decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Benzo(a)pyrene	affects methylation	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	affects cotreatment, decreases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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