ROGDI

Summary

ROGDI (rogdi atypical leucine zipper, HGNC:29478) is a protein-coding gene on chromosome 16p13.3, encoding Protein rogdi homolog (Q9GZN7).

Involved in brain development; neurogenesis; and odontogenesis of dentin-containing tooth. Located in nuclear envelope. Implicated in Kohlschutter-Tonz syndrome.

Source: NCBI Gene 79641 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amelocerebrohypohidrotic syndrome (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 652 total — 30 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 30
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_024589

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29478
Approved symbol	ROGDI
Name	rogdi atypical leucine zipper
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22386, ROGD1, RAV2
Ensembl gene	ENSG00000067836
Ensembl biotype	protein_coding
OMIM	614574
Entrez	79641

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 20 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000322048, ENST00000585653, ENST00000585871, ENST00000586153, ENST00000586336, ENST00000586504, ENST00000587377, ENST00000587711, ENST00000587843, ENST00000588201, ENST00000589543, ENST00000590198, ENST00000591292, ENST00000591392, ENST00000592019, ENST00000592112, ENST00000907804, ENST00000907805, ENST00000907806, ENST00000907807, ENST00000907808, ENST00000907809, ENST00000907810, ENST00000907811, ENST00000912071, ENST00000912072, ENST00000912073, ENST00000968425, ENST00000968426, ENST00000968427

RefSeq mRNA: 1 — MANE Select: NM_024589 NM_024589

CCDS: CCDS10523

Canonical transcript exons

ENST00000322048 — 11 exons

Exon	Start	End
ENSE00002790124	4796968	4797501
ENSE00003467401	4797938	4797987
ENSE00003512061	4800498	4800578
ENSE00003530205	4799686	4799781
ENSE00003535100	4801267	4801321
ENSE00003538653	4798569	4798667
ENSE00003573743	4798071	4798184
ENSE00003586978	4797714	4797840
ENSE00003596220	4802382	4802453
ENSE00003658479	4801503	4801585
ENSE00003903916	4802527	4802633

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.9064 / max 431.3695, expressed in 1791 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156125	13.4795	1754
156127	2.7648	1069
156129	1.1594	729
156121	0.6908	95
156124	0.5522	247
156128	0.5261	292
156120	0.2833	119
156123	0.2149	82
156126	0.1536	53
156122	0.0817	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.93	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.85	gold quality
cerebellar hemisphere	UBERON:0002245	98.71	gold quality
cerebellar cortex	UBERON:0002129	98.69	gold quality
right frontal lobe	UBERON:0002810	98.40	gold quality
spinal cord	UBERON:0002240	98.38	gold quality
apex of heart	UBERON:0002098	98.14	gold quality
cerebellum	UBERON:0002037	98.12	gold quality
prefrontal cortex	UBERON:0000451	98.10	gold quality
anterior cingulate cortex	UBERON:0009835	97.71	gold quality
cingulate cortex	UBERON:0003027	97.68	gold quality
caudate nucleus	UBERON:0001873	97.38	gold quality
putamen	UBERON:0001874	97.35	gold quality
nucleus accumbens	UBERON:0001882	97.27	gold quality
inferior vagus X ganglion	UBERON:0005363	97.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.14	gold quality
amygdala	UBERON:0001876	96.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.78	gold quality
hypothalamus	UBERON:0001898	96.74	gold quality
frontal cortex	UBERON:0001870	96.69	gold quality
adenohypophysis	UBERON:0002196	96.51	gold quality
right adrenal gland	UBERON:0001233	96.48	gold quality
right adrenal gland cortex	UBERON:0035827	96.48	gold quality
neocortex	UBERON:0001950	96.33	gold quality
lateral globus pallidus	UBERON:0002476	96.23	gold quality
heart left ventricle	UBERON:0002084	96.16	gold quality
subthalamic nucleus	UBERON:0001906	96.12	gold quality
pituitary gland	UBERON:0000007	96.10	gold quality
brain	UBERON:0000955	96.07	gold quality
monocyte	CL:0000576	96.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting ROGDI, 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-4425	100.00	67.59	1049
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-6769A-5P	97.99	64.16	851
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-3907	96.76	65.04	662
HSA-MIR-3162-5P	95.67	67.53	794

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 5)

• The finding that ROGDI mutations cause Kohlschutter-Tonz Syndrome indicates that the protein product of this gene plays an important role in neuronal development as well as amelogenesis. (PMID:22424600)
• Homozygosity mapping localized the gene linked to Kohlschutter-Tonz syndrome to a 586,513 bp region (with a LOD score of 6.4) in chromosomal region 16p13.3. The nonsense mutation was homozygous in all affected individuals. (PMID:22482807)
• We identify novel compound heterozygous ROGDI mutations in five typical Kohlschutter-Tonz syndrome families. Other families were negative for ROGDI mutations, suggesting genetic heterogeneity of atypical forms of the disease. (PMID:23086778)
• Study provides structural insights into how certain mutations in Rogdi affect its structure and cause Kohlschutter-Tonz syndrome, which has important implications for the development of pharmaceutical agents against this debilitating neurological disease. (PMID:28638151)
• Kohlschutter-Tonz syndrome (amelo-cerebro-hypohidrotic syndrome) in an Indian family with a novel ROGD1 mutation. (PMID:37646740)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rogdi	ENSDARG00000104413
mus_musculus	Rogdi	ENSMUSG00000022540
rattus_norvegicus	Rogdi	ENSRNOG00000003125
drosophila_melanogaster	rogdi	FBGN0036697
caenorhabditis_elegans		WBGENE00019196

Protein

Protein identifiers

Protein rogdi homolog — Q9GZN7 (reviewed: Q9GZN7)

All UniProt accessions (9): Q9GZN7, K7EID1, K7EJ96, K7EL91, K7EMJ5, K7EPN1, K7EPS3, K7ERN3, K7ERP1

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Monomer.

Subcellular location. Nucleus envelope. Presynapse. Cell projection. Axon. Perikaryon. Dendrite. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle.

Tissue specificity. Widely expressed with highest levels in spinal cord, brain, heart and bone marrow. Also expressed in fetal brain and liver.

Disease relevance. Kohlschuetter-Toenz syndrome (KTZS) [MIM:226750] An autosomal recessive disorder characterized by severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting both primary and secondary teeth and causing yellow or brown discoloration of the teeth. Although the phenotype is consistent, there is variability. Intellectual disability is related to the severity of seizures, and the disorder can thus be considered an epileptic encephalopathy. Some infants show normal development until seizure onset, whereas others are delayed from birth. The most severely affected individuals have profound intellectual disability, never acquire speech, and become bedridden early in life. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the rogdi family.

RefSeq proteins (1): NP_078865* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028241	RAVE2/Rogdi	Family

Pfam: PF10259

UniProt features (29 total): strand 10, helix 7, sequence variant 4, sequence conflict 2, mutagenesis site 2, initiator methionine 1, chain 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5XQH	X-RAY DIFFRACTION	2.04
5XQI	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZN7-F1	89.59	0.73

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): 2

Mutagenesis-validated functional residues (2):

Position	Phenotype
261	decreased protein stability.
271	decreased protein stability.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 247 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_MEMORY, GOBP_COGNITION, GOBP_BEHAVIOR, NKX25_02, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_NEUROGENESIS, GOBP_TOOTH_MINERALIZATION, GGGTGGRR_PAX4_03, CHANDRAN_METASTASIS_DN, CEBP_Q2, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_ENAMEL_MINERALIZATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2

GO Biological Process (19): brain development (GO:0007420), memory (GO:0007613), positive regulation of cell population proliferation (GO:0008284), response to xenobiotic stimulus (GO:0009410), gene expression (GO:0010467), neurogenesis (GO:0022008), hemopoiesis (GO:0030097), bone mineralization (GO:0030282), locomotion (GO:0040011), odontogenesis of dentin-containing tooth (GO:0042475), locomotor rhythm (GO:0045475), pH reduction (GO:0045851), neuromuscular process (GO:0050905), enamel mineralization (GO:0070166), regulation of pH (GO:0006885), locomotory behavior (GO:0007626), circadian behavior (GO:0048512), nervous system process (GO:0050877), amelogenesis (GO:0097186)

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

GO Cellular Component (12): nuclear envelope (GO:0005635), synaptic vesicle (GO:0008021), axon (GO:0030424), dendrite (GO:0030425), perikaryon (GO:0043204), RAVE complex (GO:0043291), hippocampal mossy fiber to CA3 synapse (GO:0098686), nucleus (GO:0005634), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), synapse (GO:0045202), presynapse (GO:0098793)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
neuron projection	2
cytoplasm	2
central nervous system development	1
animal organ development	1
head development	1
learning or memory	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to chemical	1
macromolecule biosynthetic process	1
nervous system development	1
cell differentiation	1
cell development	1
ossification	1
biomineral tissue development	1
biological_process	1
odontogenesis	1
locomotory behavior	1
circadian behavior	1
regulation of pH	1
nervous system process	1
tooth mineralization	1
amelogenesis	1
monoatomic cation homeostasis	1
biological regulation	1
behavior	1
rhythmic behavior	1
circadian rhythm	1
system process	1
odontogenesis of dentin-containing tooth	1
anatomical structure formation involved in morphogenesis	1
binding	1
nucleus	1
endomembrane system	1
organelle envelope	1
exocytic vesicle	1
presynapse	1
dendritic tree	1

Protein interactions and networks

STRING

526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ROGDI	DMXL2	Q8TDJ6	722
ROGDI	COPS7A	Q9UBW8	618
ROGDI	ACOX2	Q99424	562
ROGDI	WDR7	Q9Y4E6	560
ROGDI	ABHD11	Q8NFV4	534
ROGDI	ODAPH	Q17RF5	529
ROGDI	WDR72	Q3MJ13	507
ROGDI	FAM20A	Q96MK3	506
ROGDI	CNNM4	Q6P4Q7	480
ROGDI	SLC13A5	Q86YT5	474
ROGDI	ZNHIT1	O43257	468
ROGDI	DMXL1	Q9Y485	462
ROGDI	LANCL1	O43813	460
ROGDI	SMYD4	Q8IYR2	457
ROGDI	SACK1H	Q6ZRV2	447

IntAct

27 interactions, top by confidence:

A	B	Type	Score
ATP6V1C2	ATP6V1G1	psi-mi:“MI:0914”(association)	0.640
CEP63	ROGDI	psi-mi:“MI:0915”(physical association)	0.560
ATP6V1B2	ATP6V1G1	psi-mi:“MI:0914”(association)	0.530
	ROGDI	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
ROGDI		psi-mi:“MI:0914”(association)	0.350
	FAM171A2	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
ATP6V1E1	ATP6V1D	psi-mi:“MI:0914”(association)	0.350
ATP6V1F	MID1	psi-mi:“MI:0914”(association)	0.350
ATP6V1G1	MRPL3	psi-mi:“MI:0914”(association)	0.350
ATP6V1H	ATP6V1G1	psi-mi:“MI:0914”(association)	0.350
DMXL1	LLGL1	psi-mi:“MI:0914”(association)	0.350
WDR7	DMXL2	psi-mi:“MI:0914”(association)	0.350
ROGDI	ATP2A1	psi-mi:“MI:0914”(association)	0.350
ROGDI	NUDT3	psi-mi:“MI:0914”(association)	0.350
ROGDI	DISC1	psi-mi:“MI:0915”(physical association)	0.000
DISC1	ROGDI	psi-mi:“MI:0915”(physical association)	0.000
ROGDI	CEP63	psi-mi:“MI:0915”(physical association)	0.000
ROGDI		psi-mi:“MI:0915”(physical association)	0.000
ROGDI	COPS6	psi-mi:“MI:0915”(physical association)	0.000
ROGDI	CEP126	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (50): ATP1A2 (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), DMXL1 (Affinity Capture-MS), DMXL2 (Affinity Capture-MS), WDR7 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), MYH8 (Affinity Capture-MS), MYH7 (Affinity Capture-MS), ROGDI (Affinity Capture-MS), WDR7 (Affinity Capture-MS), DMXL1 (Affinity Capture-MS), DMXL2 (Affinity Capture-MS), ATP1A2 (Affinity Capture-MS), MYH7 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS)

ESM2 similar proteins: A6QQA5, A7YWU3, B5XBP5, F5HA27, F5HF47, F5HG20, O36381, O36391, O36416, O36417, P03185, P03220, P0C6Z9, P0C866, P0CK56, P0CK57, P10191, P20402, P29882, P78543, Q03552, Q04566, Q07G87, Q1RMA6, Q20A00, Q2HR98, Q3KSP4, Q3KSR8, Q3TDK6, Q4V7D2, Q567C3, Q5BK64, Q5PQ92, Q5R7X1, Q5REJ0, Q5U2R2, Q66669, Q6DFN5, Q758A1, Q7ZVT5

Diamond homologs: Q148F6, Q3TDK6, Q4V7D2, Q5R7X1, Q7ZVT5, Q9GZN7, Q9VVE2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ROGDI	“form complex”	“RAVE complex, DMXL1 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	6	251.9×	5e-13
Insulin receptor recycling	7	166.5×	2e-13
Transferrin endocytosis and recycling	7	161.2×	2e-13
ROS and RNS production in phagocytes	7	146.9×	3e-13
Amino acids regulate mTORC1	7	87.7×	8e-12
Ion channel transport	8	48.0×	1e-11

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle lumen acidification	5	212.8×	2e-09
vacuolar acidification	6	199.8×	4e-11
regulation of macroautophagy	6	80.6×	4e-09
proton transmembrane transport	5	70.9×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	16
Uncertain significance	265
Likely benign	274
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069190	NM_024589.3(ROGDI):c.402C>A (p.Tyr134Ter)	Pathogenic
1072900	NM_024589.3(ROGDI):c.652dup (p.Arg218fs)	Pathogenic
1378437	NM_024589.3(ROGDI):c.52G>T (p.Glu18Ter)	Pathogenic
1418819	NM_024589.3(ROGDI):c.103C>T (p.Gln35Ter)	Pathogenic
1453406	NM_024589.3(ROGDI):c.581_593del (p.Ile194fs)	Pathogenic
1453951	NM_024589.3(ROGDI):c.250C>T (p.Gln84Ter)	Pathogenic
1454706	NM_024589.3(ROGDI):c.613C>T (p.Gln205Ter)	Pathogenic
1965952	NM_024589.3(ROGDI):c.208C>T (p.Gln70Ter)	Pathogenic
1997122	NM_024589.3(ROGDI):c.232C>T (p.Gln78Ter)	Pathogenic
2024107	NM_024589.3(ROGDI):c.169A>T (p.Lys57Ter)	Pathogenic
2871016	NM_024589.3(ROGDI):c.331C>T (p.Gln111Ter)	Pathogenic
2912225	NM_024589.3(ROGDI):c.152dup (p.Thr52fs)	Pathogenic
3000675	NM_024589.3(ROGDI):c.-3_45+8del	Pathogenic
31225	NM_024589.3(ROGDI):c.229_230del (p.Leu77fs)	Pathogenic
31226	NM_024589.3(ROGDI):c.286C>T (p.Gln96Ter)	Pathogenic
31228	NM_024589.3(ROGDI):c.532-2A>T	Pathogenic
31229	NM_024589.3(ROGDI):c.469C>T (p.Arg157Ter)	Pathogenic
3243368	NC_000016.10:g.(?4797440)(4802591_?)del	Pathogenic
3606336	NM_024589.3(ROGDI):c.652del (p.Arg218fs)	Pathogenic
3775229	NM_024589.3(ROGDI):c.646-2A>G	Pathogenic
3775797	NM_024589.3(ROGDI):c.63G>A (p.Trp21Ter)	Pathogenic
3777587	NM_024589.3(ROGDI):c.323G>A (p.Trp108Ter)	Pathogenic
41465	NM_024589.3(ROGDI):c.507del (p.Glu170fs)	Pathogenic
461607	NM_024589.3(ROGDI):c.340C>T (p.Gln114Ter)	Pathogenic
4710243	NM_024589.3(ROGDI):c.402C>G (p.Tyr134Ter)	Pathogenic
4725854	NM_024589.3(ROGDI):c.71_72insT (p.Asp25fs)	Pathogenic
530797	NM_024589.3(ROGDI):c.665dup (p.Ala223fs)	Pathogenic
654553	NM_024589.3(ROGDI):c.302_308dup (p.Glu104fs)	Pathogenic
946794	NM_024589.3(ROGDI):c.715_718del (p.Leu239fs)	Pathogenic
947711	NM_024589.3(ROGDI):c.117+1G>T	Pathogenic

SpliceAI

1842 predictions. Top by Δscore:

Variant	Effect	Δscore
16:4797683:C:A	donor_gain	1.0000
16:4797709:CCCA:C	donor_loss	1.0000
16:4797710:CCA:C	donor_loss	1.0000
16:4797711:CA:C	donor_loss	1.0000
16:4797712:A:C	donor_loss	1.0000
16:4797713:C:CT	donor_loss	1.0000
16:4797718:T:TA	donor_gain	1.0000
16:4797837:CTCG:C	acceptor_gain	1.0000
16:4797839:CG:C	acceptor_gain	1.0000
16:4797840:GC:G	acceptor_loss	1.0000
16:4797841:C:CA	acceptor_loss	1.0000
16:4798065:CCTCA:C	donor_loss	1.0000
16:4798066:CTCAC:C	donor_loss	1.0000
16:4798067:TCAC:T	donor_loss	1.0000
16:4798068:CA:C	donor_loss	1.0000
16:4798069:A:AC	donor_gain	1.0000
16:4798069:ACC:A	donor_loss	1.0000
16:4798070:C:CC	donor_gain	1.0000
16:4798180:ATCCG:A	acceptor_gain	1.0000
16:4798182:CCG:C	acceptor_gain	1.0000
16:4798183:CG:C	acceptor_gain	1.0000
16:4798183:CGC:C	acceptor_gain	1.0000
16:4798184:GCTGC:G	acceptor_loss	1.0000
16:4798185:C:A	acceptor_loss	1.0000
16:4798185:C:CC	acceptor_gain	1.0000
16:4798186:T:C	acceptor_loss	1.0000
16:4798564:CTGA:C	donor_loss	1.0000
16:4798565:TGAC:T	donor_loss	1.0000
16:4798566:GA:G	donor_loss	1.0000
16:4798567:A:AC	donor_gain	1.0000

AlphaMissense

1874 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:4797724:A:G	L271P	1.000
16:4797742:A:G	L265P	0.999
16:4798621:A:G	L160P	0.999
16:4798630:C:G	R157P	0.999
16:4798633:G:T	A156D	0.999
16:4798642:A:G	L153P	0.999
16:4799751:C:G	A123P	0.999
16:4799771:G:T	A116D	0.999
16:4799772:C:G	A116P	0.999
16:4800512:A:G	W108R	0.999
16:4800512:A:T	W108R	0.999
16:4802386:A:G	L38P	0.999
16:4802398:A:G	L34P	0.999
16:4802434:A:G	L22P	0.999
16:4797732:G:C	C268W	0.998
16:4797734:A:G	C268R	0.998
16:4797736:A:G	L267P	0.998
16:4797775:A:G	L254P	0.998
16:4798114:A:G	L201P	0.998
16:4798621:A:C	L160R	0.998
16:4798621:A:T	L160H	0.998
16:4798634:C:G	A156P	0.998
16:4799775:C:G	D115H	0.998
16:4801305:C:G	G73R	0.998
16:4797720:C:A	K272N	0.997
16:4797720:C:G	K272N	0.997
16:4797733:C:T	C268Y	0.997
16:4798106:A:C	Y204D	0.997
16:4798120:A:G	L199P	0.997
16:4798624:C:G	R159P	0.997

dbSNP variants (sampled 300 via entrez): RS1000029394 (16:4798419 G>A,C), RS1001039124 (16:4803289 T>C), RS1001090900 (16:4803548 C>T), RS1001181734 (16:4798847 C>G), RS1001255188 (16:4799048 G>A,T), RS1001532183 (16:4796812 C>T), RS1001764863 (16:4802799 G>A,C), RS1002098387 (16:4801814 C>T), RS1002797543 (16:4803706 T>G), RS1003176083 (16:4803501 A>C,G,T), RS1003880825 (16:4798902 C>G,T), RS1004036052 (16:4801978 C>G,T), RS1005061018 (16:4802311 G>A,C), RS1005460049 (16:4803766 A>G), RS1005512428 (16:4803926 C>A,G,T)

Disease associations

OMIM: gene MIM:614574 | disease phenotypes: MIM:226750

GenCC curated gene-disease

Disease	Classification	Inheritance
amelocerebrohypohidrotic syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
amelocerebrohypohidrotic syndrome	Definitive	AR

Mondo (1): amelocerebrohypohidrotic syndrome (MONDO:0009185)

Orphanet (1): Amelocerebrohypohidrotic syndrome (Orphanet:1946)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000682	Abnormal dental enamel morphology
HP:0000705	Amelogenesis imperfecta
HP:0000726	Dementia
HP:0000750	Delayed speech and language development
HP:0000966	Hypohidrosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001321	Cerebellar hypoplasia
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure
HP:0002119	Ventriculomegaly
HP:0002353	EEG abnormality
HP:0002376	Developmental regression
HP:0002521	Hypsarrhythmia
HP:0004322	Short stature
HP:0006286	Yellow-brown discoloration of the teeth
HP:0006297	Enamel hypoplasia
HP:0007359	Focal-onset seizure
HP:0010864	Severe intellectual disability
HP:0011073	Abnormality of dental color
HP:0031936	Delayed ability to walk
HP:0032794	Myoclonic seizure
HP:0200134	Epileptic encephalopathy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003542_157	Night sleep phenotypes	1.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537213	Kohlschutter Tonz syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
Cyclosporine	decreases expression	3
(+)-JQ1 compound	decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression, affects cotreatment	1
beta-lapachone	decreases expression	1
sulforaphane	decreases expression	1
corosolic acid	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Naled	affects expression	1
Progesterone	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04681781	Not specified	ENROLLING_BY_INVITATION	SLC13A5 Deficiency Natural History Study - Remote Only
NCT06144957	Not specified	ENROLLING_BY_INVITATION	SLC13A5 Deficiency Natural History Study - United States Only