SDR9C7

Summary

SDR9C7 (short chain dehydrogenase/reductase family 9C member 7, HGNC:29958) is a protein-coding gene on chromosome 12q13.3, encoding Short-chain dehydrogenase/reductase family 9C member 7 (Q8NEX9). Plays a crucial role in the formation of the epidermal permeability barrier.

This gene encodes a protein with similarity to the short-chain dehydrogenase/reductase (SDR) family but has not been shown to have retinoid or dehydrogenase activities.

Source: NCBI Gene 121214 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ichthyosis, congenital, autosomal recessive 13 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 13
• Clinical variants (ClinVar): 117 total — 4 pathogenic
• Phenotypes (HPO): 33
• MANE Select transcript: NM_148897

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29958
Approved symbol	SDR9C7
Name	short chain dehydrogenase/reductase family 9C member 7
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	SDR-O, RDHS
Ensembl gene	ENSG00000170426
Ensembl biotype	protein_coding
OMIM	609769
Entrez	121214

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000293502

RefSeq mRNA: 1 — MANE Select: NM_148897 NM_148897

CCDS: CCDS8926

Canonical transcript exons

ENST00000293502 — 4 exons

Exon	Start	End
ENSE00001059936	56929390	56929553
ENSE00001059937	56930226	56930484
ENSE00001142266	56923133	56924050
ENSE00001142275	56933961	56934408

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 91.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1172 / max 40.9619, expressed in 30 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131604	0.0824	26
131603	0.0348	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	91.74	gold quality
skin of abdomen	UBERON:0001416	91.47	gold quality
zone of skin	UBERON:0000014	89.58	gold quality
penis	UBERON:0000989	81.98	gold quality
esophagus mucosa	UBERON:0002469	79.92	gold quality
lower esophagus mucosa	UBERON:0035834	76.09	gold quality
vagina	UBERON:0000996	73.33	gold quality
mammalian vulva	UBERON:0000997	72.42	gold quality
upper leg skin	UBERON:0004262	72.19	gold quality
esophagus squamous epithelium	UBERON:0006920	68.42	silver quality
oral cavity	UBERON:0000167	67.13	gold quality
esophagus	UBERON:0001043	64.48	gold quality
ectocervix	UBERON:0012249	62.76	gold quality
skin of hip	UBERON:0001554	62.46	gold quality
gastrocnemius	UBERON:0001388	59.77	gold quality
muscle of leg	UBERON:0001383	58.50	gold quality
uterine cervix	UBERON:0000002	56.05	gold quality
gingiva	UBERON:0001828	56.04	gold quality
hindlimb stylopod muscle	UBERON:0004252	55.87	gold quality
body of tongue	UBERON:0011876	53.79	silver quality
right hemisphere of cerebellum	UBERON:0014890	53.51	gold quality
cerebellar hemisphere	UBERON:0002245	53.39	gold quality
cerebellar cortex	UBERON:0002129	53.29	gold quality
pharyngeal mucosa	UBERON:0000355	52.54	silver quality
cerebellum	UBERON:0002037	52.28	gold quality
tonsil	UBERON:0002372	51.70	gold quality
body of uterus	UBERON:0009853	50.94	gold quality
mucosa of stomach	UBERON:0001199	50.63	gold quality
nipple	UBERON:0002030	50.01	silver quality
heart left ventricle	UBERON:0002084	49.42	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting SDR9C7, 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-3646	100.00	73.56	5283
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-3121-5P	97.30	66.62	1146
HSA-MIR-4750-3P	96.65	64.38	512
HSA-MIR-6874-5P	95.73	64.94	545
HSA-MIR-10A-3P	93.57	64.43	451
HSA-MIR-196B-3P	85.79	67.95	91

Literature-anchored findings (GeneRIF, showing 5)

• Missense mutations in SDR9C7 gene were identified in families with autosomal recessive congenital ichthyosis: two families shared an identical homozygous mutation c.599T > C (p.Ile200Thr) and one family had another homozygous mutation c.214C > T (p.Arg72Trp). The mutations severely affected a stability of the protein. In a patient’s skin, SDR9C7 gene expression in the cornified layer was decreased. (PMID:28173123)
• The authors report a novel mutation in SDR9C7 responsible for ARCI in a Pakistani family. (PMID:28369735)
• The results strongly support the findings of previous studies,2-5 and thus provide further evidence that SDR9C7 is a novel causative gene for ARCI. (PMID:28906551)
• Next-generation sequencing through multi-gene panel testing for diagnosis of hereditary ichthyosis in Chinese. (PMID:31953843)
• Knockdown of SDR9C7 Impairs Epidermal Barrier Function. (PMID:33422619)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sdr9c7	ENSMUSG00000040127
rattus_norvegicus	Sdr9c7	ENSRNOG00000086854

Paralogs (25): HSD17B6 (ENSG00000025423), RDH11 (ENSG00000072042), HSD17B10 (ENSG00000072506), DHRS9 (ENSG00000073737), HSD17B2 (ENSG00000086696), HSD17B14 (ENSG00000087076), DHRS12 (ENSG00000102796), HSDL1 (ENSG00000103160), HSD17B1 (ENSG00000108786), RDH10 (ENSG00000121039), HSD17B3 (ENSG00000130948), HSD17B7 (ENSG00000132196), HSD17B4 (ENSG00000133835), RDH5 (ENSG00000135437), RDH16 (ENSG00000139547), RDH12 (ENSG00000139988), HSD17B12 (ENSG00000149084), BDH1 (ENSG00000161267), DHRS3 (ENSG00000162496), HSD17B13 (ENSG00000170509), SDR16C5 (ENSG00000170786), HSD11B2 (ENSG00000176387), WWOX (ENSG00000186153), HSD17B11 (ENSG00000198189), HSD17B8 (ENSG00000204228)

Protein

Protein identifiers

Short-chain dehydrogenase/reductase family 9C member 7 — Q8NEX9 (reviewed: Q8NEX9)

Alternative names: O-acylceramide dehydrogenase, Orphan short-chain dehydrogenase/reductase, RDH-S

All UniProt accessions (1): Q8NEX9

UniProt curated annotations — full annotation on UniProt →

Function. Plays a crucial role in the formation of the epidermal permeability barrier. Catalyzes the NAD+-dependent dehydrogenation of the linoleate 9,10-trans-epoxy-11E-13-alcohol esterified in omega-O-acylceramides (such as in N-[omega-(9R,10R)-epoxy-(13R)-hydroxy-(11E)-octadecenoyloxy]-acylsphing-4E-enine) to the corresponding 13-ketone, the reactive moiety required for binding of epidermal ceramides to proteins. Displays weak conversion of all-trans-retinal to all-trans-retinol in the presence of NADH. Has apparently no steroid dehydrogenase activity.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in the skin. Expressed in granular and cornified layers of the epidermis (at protein level). Highly expressed in liver.

Disease relevance. Ichthyosis, congenital, autosomal recessive 13 (ARCI13) [MIM:617574] A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family.

RefSeq proteins (1): NP_683695* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR020904	Sc_DH/Rdtase_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00106

Catalyzed reactions (Rhea), 2 shown:

• a N-[omega-(9R,10R)-epoxy-(13R)-hydroxy-(11E)-octadecenoyloxy]acyl-beta-D-glucosyl-(1<->1)-sphing-4E-enine + NAD(+) = a N-[omega-(9R,10R)-epoxy-13-oxo-(11E)-octadecenoyloxy]acyl-beta-D-glucosyl-(1<->1)-sphing-4E-enine + NADH + H(+) (RHEA:82447)
• a N-[omega-(9R,10R)-epoxy-(13R)-hydroxy-(11E)-octadecenoyloxy]-acylsphing-4E-enine + NAD(+) = a N-[omega-(9R,10R)-epoxy-13-oxo-(11E)-octadecenoyloxy]-acylsphing-4E-enine + NADH + H(+) (RHEA:82471)

UniProt features (7 total): binding site 2, sequence variant 2, chain 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEX9-F1	93.41	0.82

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 (1): 172 (proton acceptor)

Ligand- & substrate-binding residues (2): 29–53; 160

Post-translational modifications (1): 185

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2453902	The canonical retinoid cycle in rods (twilight vision)

MSigDB gene sets: 109 (showing top): GOBP_REGULATION_OF_HORMONE_LEVELS, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_RETINOL_METABOLIC_PROCESS, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_LIPID_METABOLIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, RICKMAN_HEAD_AND_NECK_CANCER_C, GOBP_ISOPRENOID_METABOLIC_PROCESS, GOBP_PRIMARY_ALCOHOL_METABOLIC_PROCESS, GOBP_STEROID_METABOLIC_PROCESS, GOBP_ALCOHOL_METABOLIC_PROCESS

GO Biological Process (2): steroid metabolic process (GO:0008202), retinol metabolic process (GO:0042572)

GO Molecular Function (3): all-trans-retinol dehydrogenase (NAD+) activity (GO:0004745), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616)

GO Cellular Component (1): cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Visual phototransduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	1
retinoid metabolic process	1
primary alcohol metabolic process	1
hormone metabolic process	1
olefinic compound metabolic process	1
alcohol dehydrogenase (NAD+) activity	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

596 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDR9C7	PNPLA1	Q8N8W4	724
SDR9C7	CYP4F22	Q6NT55	702
SDR9C7	LRAT	O95237	700
SDR9C7	NIPAL4	Q0D2K0	685
SDR9C7	ALOXE3	Q9BYJ1	663
SDR9C7	SORD	Q00796	656
SDR9C7	ALOX12B	O75342	655
SDR9C7	ABCA12	Q86UK0	631
SDR9C7	CERS3	Q8IU89	618
SDR9C7	RBP1	P09455	616
SDR9C7	RDH14	Q9HBH5	611
SDR9C7	RPE65	Q16518	608
SDR9C7	SULT2B1	O00204	595
SDR9C7	CYP26A1	O43174	593
SDR9C7	STRA6	Q9BX79	586

IntAct

98 interactions, top by confidence:

A	B	Type	Score
ASH2L	KMT2D	psi-mi:“MI:0914”(association)	0.890
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
CCNC	MED19	psi-mi:“MI:0914”(association)	0.640
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
DNAAF19	KLK10	psi-mi:“MI:0914”(association)	0.530
AIRE	ALOX12B	psi-mi:“MI:0914”(association)	0.530
DPPA4	ALOX12B	psi-mi:“MI:0914”(association)	0.530
NDUFS5	NDUFS4	psi-mi:“MI:0914”(association)	0.530
ZIC1	CTSV	psi-mi:“MI:0914”(association)	0.530
CLINT1	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
CXCL1	SDR9C7	psi-mi:“MI:0915”(physical association)	0.400
SDR9C7	TRPC4AP	psi-mi:“MI:0915”(physical association)	0.400
CFTR	SDR9C7	psi-mi:“MI:0915”(physical association)	0.370
PI4KA	A2ML1	psi-mi:“MI:0914”(association)	0.350
VAV1	CHEK1	psi-mi:“MI:0914”(association)	0.350
FCF1	SULT2B1	psi-mi:“MI:0914”(association)	0.350
HSF2	IMPA2	psi-mi:“MI:0914”(association)	0.350
ZIC1	IMPA2	psi-mi:“MI:0914”(association)	0.350
RBFOX1	IMPA2	psi-mi:“MI:0914”(association)	0.350
PLK2	ANKRD28	psi-mi:“MI:0914”(association)	0.350
KLHL11	PIPSL	psi-mi:“MI:0914”(association)	0.350
OR13C3	POTEF	psi-mi:“MI:0914”(association)	0.350
BEX5	A2ML1	psi-mi:“MI:0914”(association)	0.350
TLR7	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (91): SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS)

ESM2 similar proteins: A4IFM3, A5JYX5, A7LB60, B8A5W4, O14756, O54753, O54939, O88451, P0DKC5, P0DKC6, P0DKC7, P17636, P29147, P50170, P55006, P97501, Q02337, Q02338, Q05A13, Q0IH28, Q0VFE7, Q3SXM5, Q3T001, Q566S6, Q58NB6, Q5R7K0, Q5RJY4, Q6IAN0, Q7TQA3, Q80XN0, Q8HYR6, Q8K3P0, Q8K4B7, Q8L9C4, Q8N3Y7, Q8N5I4, Q8NEX9, Q8TC12, Q8VD48, Q8VHG0

Diamond homologs: A0A017SE81, A0A023I4F1, A0A0E3D8L9, A0A0U1LQE2, A0A140JWS5, A0A1L5BU05, A0A1U8QWA2, A0A1V6PAN1, A0A5B8YU68, A3F5F0, A4IFM3, B6H062, C8WJW0, D4Z260, F1QLP1, G9N4A9, O14351, O14756, O54909, O55240, O75452, O88451, P07999, P0CU71, P10528, P12310, P29147, P37059, P39482, P39483, P39484, P39485, P40288, P50170, P51658, P54554, P55006, Q02337, Q02338, Q09851

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	71
Likely benign	22
Benign	7

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
4281535	NM_148897.3(SDR9C7):c.560+1G>A	Pathogenic
430712	NM_148897.3(SDR9C7):c.214C>T (p.Arg72Trp)	Pathogenic
488591	NM_148897.3(SDR9C7):c.658C>T (p.Arg220Ter)	Pathogenic
520397	NM_148897.3(SDR9C7):c.364dup (p.Thr122fs)	Pathogenic

SpliceAI

676 predictions. Top by Δscore:

Variant	Effect	Δscore
12:56924051:C:CC	acceptor_gain	1.0000
12:56924051:C:T	acceptor_loss	1.0000
12:56924052:T:G	acceptor_loss	1.0000
12:56929386:TTAC:T	donor_loss	1.0000
12:56929388:A:AC	donor_gain	1.0000
12:56929388:A:AT	donor_loss	1.0000
12:56929389:C:CA	donor_gain	1.0000
12:56929389:CA:C	donor_gain	1.0000
12:56929389:CAG:C	donor_gain	1.0000
12:56929389:CAGA:C	donor_gain	1.0000
12:56929389:CAGAT:C	donor_gain	1.0000
12:56929549:CACGC:C	acceptor_gain	1.0000
12:56929550:ACGC:A	acceptor_gain	1.0000
12:56929551:CGC:C	acceptor_gain	1.0000
12:56929551:CGCC:C	acceptor_gain	1.0000
12:56929552:GC:G	acceptor_gain	1.0000
12:56929552:GCC:G	acceptor_loss	1.0000
12:56929553:CC:C	acceptor_gain	1.0000
12:56929554:C:A	acceptor_loss	1.0000
12:56929554:C:CC	acceptor_gain	1.0000
12:56929554:C:T	acceptor_gain	1.0000
12:56933985:CCCA:C	donor_gain	1.0000
12:56933988:A:AC	donor_gain	1.0000
12:56933989:C:CC	donor_gain	1.0000
12:56923902:AG:A	donor_gain	0.9900
12:56924047:GTAT:G	acceptor_gain	0.9900
12:56924048:TAT:T	acceptor_gain	0.9900
12:56924055:T:C	acceptor_gain	0.9900
12:56929383:AACTT:A	donor_loss	0.9900
12:56929384:ACTTA:A	donor_loss	0.9900

AlphaMissense

2040 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:56930239:A:G	S183P	0.997
12:56930255:A:C	F177L	0.997
12:56930255:A:T	F177L	0.997
12:56930257:A:G	F177L	0.997
12:56930262:G:A	S175F	0.997
12:56930428:A:G	W120R	0.997
12:56930428:A:T	W120R	0.997
12:56930465:G:C	N107K	0.997
12:56930465:G:T	N107K	0.997
12:56930226:C:A	R187M	0.996
12:56930262:G:T	S175Y	0.996
12:56930272:A:G	Y172H	0.996
12:56930226:C:G	R187T	0.995
12:56930319:A:T	V156D	0.995
12:56934163:A:C	C33W	0.995
12:56930238:G:A	S183F	0.994
12:56930315:G:C	N157K	0.994
12:56930315:G:T	N157K	0.994
12:56930343:A:T	V148D	0.994
12:56930387:G:C	N133K	0.994
12:56930387:G:T	N133K	0.994
12:56930306:G:C	S160R	0.993
12:56930306:G:T	S160R	0.993
12:56930308:T:G	S160R	0.993
12:56930385:A:G	L134P	0.993
12:56934164:C:T	C33Y	0.993
12:56934179:A:T	V28D	0.993
12:56929553:C:A	R187S	0.992
12:56929553:C:G	R187S	0.992
12:56930240:G:C	F182L	0.992

dbSNP variants (sampled 300 via entrez): RS1000083970 (12:56932836 A>G), RS1000226111 (12:56928935 C>T), RS1000389090 (12:56926238 C>A), RS1000458918 (12:56935445 C>T), RS1000501566 (12:56923827 C>T), RS1000788422 (12:56936303 A>G), RS1000852521 (12:56935202 C>G), RS1001293733 (12:56935685 A>C), RS1001598693 (12:56923288 A>T), RS1001722671 (12:56926157 A>G), RS1001732934 (12:56932150 T>C), RS1001933826 (12:56924826 C>T), RS1002110085 (12:56930602 G>A,C,T), RS1002565932 (12:56930889 A>G), RS1002625918 (12:56924801 A>G)

Disease associations

OMIM: gene MIM:609769 | disease phenotypes: MIM:617574, MIM:615274, MIM:615486, MIM:616280, MIM:616917

GenCC curated gene-disease

Disease	Classification	Inheritance
ichthyosis, congenital, autosomal recessive 13	Strong	Autosomal recessive
lamellar ichthyosis	Supportive	Autosomal recessive

Mondo (6): ichthyosis, congenital, autosomal recessive 13 (MONDO:0033092), cataract 15 multiple types (MONDO:0014110), severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (MONDO:0014206), Charcot-Marie-Tooth disease axonal type 2U (MONDO:0014566), lamellar ichthyosis (MONDO:0017778), intellectual disability, autosomal recessive 53 (MONDO:0014832)

Orphanet (5): Autosomal dominant Charcot-Marie-Tooth disease type 2U (Orphanet:397735), Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (Orphanet:440427), Early onset non-syndromic cataract (Orphanet:91492), Lamellar ichthyosis (Orphanet:313), Early-onset epilepsy-intellectual disability-brain anomalies syndrome (Orphanet:488635)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000164	Abnormality of the dentition
HP:0000232	Everted lower lip vermilion
HP:0000365	Hearing impairment
HP:0000389	Chronic otitis media
HP:0000491	Keratitis
HP:0000656	Ectropion
HP:0000958	Dry skin
HP:0000962	Hyperkeratosis
HP:0000966	Hypohidrosis
HP:0000972	Palmoplantar hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0000989	Pruritus
HP:0001019	Erythroderma
HP:0001508	Failure to thrive
HP:0001596	Alopecia
HP:0001597	Abnormal nail morphology
HP:0001944	Dehydration
HP:0002205	Recurrent respiratory infections
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0008064	Ichthyosis
HP:0008070	Sparse hair
HP:0011039	Abnormal helix morphology
HP:0012203	Onychomycosis
HP:0025114	Hypergranulosis
HP:0100543	Cognitive impairment
HP:0100679	Lack of skin elasticity
HP:0100758	Gangrene

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002775_4	Alzheimer’s disease (survival time)	2.000000e-06
GCST003720_17	Migraine	1.000000e-09
GCST003720_20	Migraine	6.000000e-49
GCST003721_7	Migraine without aura	4.000000e-16
GCST005337_1	Headache	5.000000e-47
GCST006086_3	Familial lung cancer	4.000000e-07
GCST006904_13	Cerebral amyloid deposition (PET imaging)	7.000000e-06
GCST007564_27	Asthma or allergic disease (pleiotropy)	8.000000e-13
GCST008849_4	Depressive symptoms (binary sum-score)	4.000000e-08
GCST008916_110	Asthma	1.000000e-27
GCST008916_18	Asthma	8.000000e-18
GCST008916_2	Asthma	2.000000e-08
GCST010002_217	Refractive error	6.000000e-174

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0000714	survival time
EFO:0006953	family history of lung cancer
EFO:0007707	cerebral amyloid deposition measurement
EFO:0007006	depressive symptom measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenate	decreases expression, increases abundance	1
arsenite	decreases expression, increases abundance	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sodium arsenite	decreases expression, increases abundance	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	increases expression	1
hydroquinone	increases expression	1
perfluorooctane sulfonic acid	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluorohexanesulfonic acid	affects cotreatment, increases expression	1
abrine	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Lead	affects methylation	1
Methapyrilene	increases methylation	1
NAD	affects binding, increases activity	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01222000	PHASE3	UNKNOWN	Treatment of the Recessive Nonbullous Congenital Ichthyosis by the Epigallocatechine Cutaneous
NCT03041038	PHASE2	COMPLETED	The Efficacy and Safety of Secukinumab in Patients With Ichthyoses
NCT03738800	PHASE2	TERMINATED	A Safety, Efficacy and Systemic Exposure Study of CD5789 Cream in Adults and Adolescents With Lamellar Ichthyosis
NCT00001292	Not specified	COMPLETED	Study of Scaling Disorders and Other Inherited Skin Diseases
NCT05514470	Not specified	WITHDRAWN	Impact of Mutations in Aminoacyl tRNA Synthetases on Protein Translation and Cellular Stress