MID2

Summary

MID2 (midline 2, HGNC:7096) is a protein-coding gene on chromosome Xq22.3, encoding Probable E3 ubiquitin-protein ligase MID2 (Q9UJV3). E3 ubiquitin ligase that plays a role in microtubule stabilization.

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to microtubular structures in the cytoplasm. Alternate splicing of this gene results in two transcript variants encoding different isoforms.

Source: NCBI Gene 11043 — RefSeq curated summary.

At a glance

• Gene–disease (curated): non-syndromic X-linked intellectual disability (Supportive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 63 total
• Phenotypes (HPO): 14
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_012216

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7096
Approved symbol	MID2
Name	midline 2
Location	Xq22.3
Locus type	gene with protein product
Status	Approved
Aliases	FXY2, TRIM1, RNF60, MRX101
Ensembl gene	ENSG00000080561
Ensembl biotype	protein_coding
OMIM	300204
Entrez	11043

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000262843, ENST00000443968, ENST00000451923, ENST00000474517, ENST00000898670, ENST00000921443

RefSeq mRNA: 4 — MANE Select: NM_012216 NM_001382751, NM_001382752, NM_012216, NM_052817

CCDS: CCDS14532, CCDS14533

Canonical transcript exons

ENST00000262843 — 10 exons

Exon	Start	End
ENSE00001434860	107917506	107917739
ENSE00001617216	107916002	107916129
ENSE00001635020	107905478	107905626
ENSE00001649333	107926094	107926301
ENSE00001735565	107854609	107854704
ENSE00001749739	107840670	107841385
ENSE00001768609	107903958	107904065
ENSE00001860554	107825866	107826430
ENSE00003672631	107924343	107924504
ENSE00003905678	107926671	107931637

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 86.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.1044 / max 25.5710, expressed in 1121 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197188	2.4757	1041
197187	0.3643	193
197186	0.2644	93

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	86.93	gold quality
islet of Langerhans	UBERON:0000006	84.91	gold quality
cartilage tissue	UBERON:0002418	84.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.62	gold quality
lower esophagus mucosa	UBERON:0035834	84.19	gold quality
muscle of leg	UBERON:0001383	83.48	gold quality
smooth muscle tissue	UBERON:0001135	83.26	gold quality
gastrocnemius	UBERON:0001388	83.24	gold quality
upper leg skin	UBERON:0004262	83.17	gold quality
pancreatic ductal cell	CL:0002079	82.90	gold quality
popliteal artery	UBERON:0002250	81.99	gold quality
tibial artery	UBERON:0007610	81.98	gold quality
skeletal muscle organ	UBERON:0014892	81.72	gold quality
muscle organ	UBERON:0001630	81.71	gold quality
skin of leg	UBERON:0001511	81.67	gold quality
epithelium of esophagus	UBERON:0001976	81.09	gold quality
esophagus squamous epithelium	UBERON:0006920	81.03	gold quality
zone of skin	UBERON:0000014	81.01	gold quality
vagina	UBERON:0000996	80.87	gold quality
lower esophagus	UBERON:0013473	80.82	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.79	gold quality
adrenal tissue	UBERON:0018303	80.74	gold quality
gall bladder	UBERON:0002110	80.69	gold quality
aorta	UBERON:0000947	80.58	gold quality
skin of abdomen	UBERON:0001416	80.57	gold quality
left adrenal gland	UBERON:0001234	80.53	gold quality
ectocervix	UBERON:0012249	80.34	gold quality
calcaneal tendon	UBERON:0003701	80.28	gold quality
cervix squamous epithelium	UBERON:0006922	80.25	silver quality
diaphragm	UBERON:0001103	80.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.05

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
JUN	Activation

miRNA regulators (miRDB)

232 targeting MID2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-12136	99.98	72.81	5713

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 8)

• MID2 coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the MID-alpha 4 complex with microtubules. (PMID:11806752)
• MID2 is a candidate gene for FG syndrome. (PMID:16283679)
• A novel missense mutation (c.1040G>A, p.Arg347Gln) was reported in MID2, which encodes ubiquitin ligase E3, as the likely cause of X-linked mental retardation in a large kindred. (PMID:24115387)
• Mid2 regulates cell division through the ubiquitination of astrin on K409, which is critical for its degradation and proper cytokinesis. (PMID:26748699)
• overexpressed in advanced breast cancer and high overexpression is prognostic factor for poor overall survival (PMID:26791755)
• The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity. (PMID:35266954)
• Expanding the genetic and phenotypic spectrum of TRAPPC9 and MID2-related neurodevelopmental disabilities: report of two novel mutations, 3D-modelling, and molecular docking studies. (PMID:38467738)
• CircTRIM1 encodes TRIM1-269aa to promote chemoresistance and metastasis of TNBC via enhancing CaM-dependent MARCKS translocation and PI3K/AKT/mTOR activation. (PMID:38755678)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mid2	ENSDARG00000034871
mus_musculus	Mid2	ENSMUSG00000000266
rattus_norvegicus	Mid2	ENSRNOG00000060542

Paralogs (80): TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), TRIM3 (ENSG00000110171), TRIM38 (ENSG00000112343), TRIM62 (ENSG00000116525), TRIM67 (ENSG00000119283), TRIM32 (ENSG00000119401), BSPRY (ENSG00000119411), TRIM25 (ENSG00000121060), TRIM6 (ENSG00000121236), TRIM24 (ENSG00000122779), TRIM51 (ENSG00000124900), TRIM28 (ENSG00000130726), TRIM21 (ENSG00000132109), TRIM5 (ENSG00000132256), TRIM22 (ENSG00000132274), TRIM47 (ENSG00000132481), TRIM45 (ENSG00000134253), TRIM29 (ENSG00000137699), TRIM54 (ENSG00000138100), PML (ENSG00000140464), TRIM65 (ENSG00000141569), TRIM43B (ENSG00000144010), TRIM43 (ENSG00000144015), TRIM7 (ENSG00000146054), TRIM41 (ENSG00000146063), TRIM50 (ENSG00000146755), TRIM4 (ENSG00000146833), TRIM55 (ENSG00000147573), TRIM48 (ENSG00000150244), TRIM36 (ENSG00000152503), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

Probable E3 ubiquitin-protein ligase MID2 — Q9UJV3 (reviewed: Q9UJV3)

Alternative names: Midin-2, Midline defect 2, Midline-2, RING finger protein 60, RING-type E3 ubiquitin transferase MID2, Tripartite motif-containing protein 1

All UniProt accessions (2): Q9UJV3, A6PVI4

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin ligase that plays a role in microtubule stabilization. Mediates the ‘Lys-48’-linked polyubiquitination of LRRK2 to drive its localization to microtubules and its proteasomal degradation in neurons. This ubiquitination inhibits LRRK2 kinase activation by RAB29.

Subunit / interactions. Homodimer or heterodimer with MID1. Interacts with IGBP1.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Low level in fetal kidney and lung, and in adult prostate, ovary and small intestine.

Post-translational modifications. Phosphorylated on serine and threonine residues.

Disease relevance. Intellectual developmental disorder, X-linked 101 (XLID101) [MIM:300928] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. XLID101 clinical features include global developmental delay, hyperactivity often with aggressive outbursts, and seizures in some patients. Several affected individuals have long face, prominent ears, and squint or strabismus. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The tripartite motif (RBCC; RING- and B box-type zinc fingers and coiled coil domains) mediates dimerization. Associates with microtubules in a manner that is dependent on the C-terminal B30.2 domain.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UJV3-1	1	yes
Q9UJV3-2	2

RefSeq proteins (4): NP_001369680, NP_001369681, NP_036348, NP_438112 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR001870	B30.2/SPRY	Domain
IPR003649	Bbox_C	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR003961	FN3_dom	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017903	COS_domain	Domain
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR033491	MID2_HC-RING	Domain
IPR035752	SPRY/PRY_TRIM1	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR040859	Midline-1_COS	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR047063	MID2_Bbox2_Zfn	Domain
IPR047064	MID2_Bbox1_Zfn	Domain
IPR050617	E3_ligase_FN3/SPRY	Family

Pfam: PF00041, PF00622, PF00643, PF13445, PF18568, PF22586

UniProt features (46 total): strand 23, binding site 4, helix 4, domain 3, sequence variant 3, turn 3, zinc finger region 3, chain 1, splice variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7QRZ	X-RAY DIFFRACTION	1.57
9R11	X-RAY DIFFRACTION	1.64
2DJA	SOLUTION NMR
2DMK	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJV3-F1	80.18	0.47

Functional residue map

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

Ligand- & substrate-binding residues (4): 218; 224; 195; 198

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_REGULATION_OF_AUTOPHAGY, JAEGER_METASTASIS_DN, GCANCTGNY_MYOD_Q6, GOZGIT_ESR1_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, AP4_Q6, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, MILI_PSEUDOPODIA_HAPTOTAXIS_UP

GO Biological Process (11): positive regulation of autophagy (GO:0010508), negative regulation of viral transcription (GO:0032897), protein localization to microtubule (GO:0035372), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), suppression of viral release by host (GO:0044790), innate immune response (GO:0045087), host-mediated suppression of symbiont invasion (GO:0046597), protein K48-linked ubiquitination (GO:0070936), protein ubiquitination (GO:0016567), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of intracellular signal transduction (GO:1902533)

GO Molecular Function (11): transcription coactivator activity (GO:0003713), microtubule binding (GO:0008017), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), phosphoprotein binding (GO:0051219), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), microtubule (GO:0005874), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
viral transcription	1
regulation of viral transcription	1
negative regulation of viral process	1
protein localization to microtubule cytoskeleton	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
defense response to virus	1
immune response	1
defense response to symbiont	1
innate immune response	1
host-mediated perturbation of symbiont process	1
protein polyubiquitination	1
protein modification by small protein conjugation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of signal transduction	1
intracellular signal transduction	1
regulation of intracellular signal transduction	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
tubulin binding	1
transition metal ion binding	1
identical protein binding	1
protein dimerization activity	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
extracellular vesicle	1

Protein interactions and networks

STRING

704 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MID2	PRPS1L1	P21108	775
MID2	BBOX1	O75936	773
MID2	COL4A6	Q14031	760
MID2	PRPS1	P09329	743
MID2	PRPS2	P11908	717
MID2	TRAT1	Q6PIZ9	661
MID2	ROM1	Q03395	591
MID2	TRIM27	P14373	582
MID2	TRIM5	Q9C035	582
MID2	BRCA1	P38398	576
MID2	TMLHE	Q9NVH6	479
MID2	PML	P29590	465
MID2	MID1	O15344	451
MID2	RD3	Q7Z3Z2	442
MID2	TRIM66	O15016	407

IntAct

60 interactions, top by confidence:

A	B	Type	Score
IGBP1	PPP2CA	psi-mi:“MI:0914”(association)	0.960
LRRK2	YWHAQ	psi-mi:“MI:0914”(association)	0.910
GMNN	MCIDAS	psi-mi:“MI:0914”(association)	0.770
MID2	LRRK2	psi-mi:“MI:0915”(physical association)	0.600
MID2	LRRK2	psi-mi:“MI:0403”(colocalization)	0.600
LRRK2	MID2	psi-mi:“MI:0915”(physical association)	0.600
MID2	UTP25	psi-mi:“MI:0915”(physical association)	0.550
MID2	ZNF24	psi-mi:“MI:0915”(physical association)	0.550
MID2	UBE2D4	psi-mi:“MI:0915”(physical association)	0.550
ZNF24	MID2	psi-mi:“MI:0915”(physical association)	0.550
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
GSTT1	MID1	psi-mi:“MI:0914”(association)	0.530
SYT17	TF	psi-mi:“MI:0914”(association)	0.530
rep	NKRF	psi-mi:“MI:0914”(association)	0.500
MID2	gB	psi-mi:“MI:0915”(physical association)	0.370
MID2		psi-mi:“MI:0915”(physical association)	0.370
MID2	UNC45A	psi-mi:“MI:0915”(physical association)	0.370
MID2	LGALS14	psi-mi:“MI:0915”(physical association)	0.370
MID2	ZNF774	psi-mi:“MI:0915”(physical association)	0.370
MID2	NR1D2	psi-mi:“MI:0915”(physical association)	0.370
MID2	SCNM1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (408): MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid), MID2 (Two-hybrid)

ESM2 similar proteins: A1L4K1, D4A7V9, E9QHE3, F1LW30, H0UZ81, O15344, O70583, O95361, P82457, P82458, P97573, Q14258, Q14596, Q28CB1, Q38HM4, Q3UMR0, Q3V3A7, Q58D15, Q5F479, Q5R760, Q5RC94, Q5REJ9, Q5REW9, Q5RF77, Q5XIH6, Q61510, Q6P549, Q6P6S3, Q6UXZ4, Q7T2L7, Q7TNH6, Q7Z494, Q80VK6, Q80WG7, Q8BZ52, Q8JZL1, Q8K1S2, Q8NFM7, Q91Z63, Q969Q1

Diamond homologs: A0A3B3IT33, A0JN74, A2XK56, A4QPC6, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NLI5, A6NLU0, B1H278, B8B5U8, C9J1S8, D3YY23, D3Z8N2, F8VTS6, I1YAP6, O00478, O00481, O13033, O54952, O60106, O76064, P0CI25, P0CI26, P18892, P19474, P38398, P48754, P82456, P86448, P86449, Q14258, Q14527, Q1XHT8, Q28DS3, Q2HJ46, Q3C1V9, Q3TL54, Q4KLN8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	MID2	ubiquitination
MID2	“down-regulates quantity by destabilization”	SPAG5	ubiquitination
MID2	“down-regulates quantity by destabilization”	LRRK2	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1673 predictions. Top by Δscore:

Variant	Effect	Δscore
X:107840667:CA:C	acceptor_loss	1.0000
X:107840668:A:AG	acceptor_gain	1.0000
X:107840668:AGGT:A	acceptor_gain	1.0000
X:107840669:G:A	acceptor_loss	1.0000
X:107840669:G:GG	acceptor_gain	1.0000
X:107840669:GGT:G	acceptor_gain	1.0000
X:107840669:GGTG:G	acceptor_gain	1.0000
X:107841382:CAAGG:C	donor_loss	1.0000
X:107841383:AAGGT:A	donor_loss	1.0000
X:107841386:GT:G	donor_loss	1.0000
X:107841387:T:G	donor_loss	1.0000
X:107854573:G:A	acceptor_gain	1.0000
X:107854583:T:TA	acceptor_gain	1.0000
X:107854584:G:A	acceptor_gain	1.0000
X:107854700:TTG:T	donor_gain	1.0000
X:107903952:TGGCA:T	acceptor_loss	1.0000
X:107903953:GGCA:G	acceptor_loss	1.0000
X:107903954:GCA:G	acceptor_loss	1.0000
X:107903955:CA:C	acceptor_loss	1.0000
X:107903956:A:AC	acceptor_loss	1.0000
X:107903957:G:GT	acceptor_loss	1.0000
X:107903957:GGTGA:G	acceptor_gain	1.0000
X:107904061:CAAAG:C	donor_loss	1.0000
X:107904062:AAAG:A	donor_loss	1.0000
X:107904063:AAGGT:A	donor_loss	1.0000
X:107904064:AGGT:A	donor_loss	1.0000
X:107904067:T:A	donor_loss	1.0000
X:107905466:A:AG	acceptor_gain	1.0000
X:107905624:GAG:G	donor_gain	1.0000
X:107905625:AGG:A	donor_loss	1.0000

AlphaMissense

4894 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:107840748:T:C	L28S	1.000
X:107840748:T:G	L28W	1.000
X:107840753:T:A	C30S	1.000
X:107840753:T:C	C30R	1.000
X:107840753:T:G	C30G	1.000
X:107840754:G:A	C30Y	1.000
X:107840754:G:C	C30S	1.000
X:107840754:G:T	C30F	1.000
X:107840755:T:G	C30W	1.000
X:107840757:C:A	P31Q	1.000
X:107840762:T:A	C33S	1.000
X:107840762:T:C	C33R	1.000
X:107840763:G:A	C33Y	1.000
X:107840763:G:C	C33S	1.000
X:107840764:C:G	C33W	1.000
X:107840766:T:C	L34P	1.000
X:107840774:T:C	F37L	1.000
X:107840775:T:C	F37S	1.000
X:107840775:T:G	F37C	1.000
X:107840776:T:A	F37L	1.000
X:107840776:T:G	F37L	1.000
X:107840783:C:T	P40S	1.000
X:107840784:C:A	P40H	1.000
X:107840784:C:G	P40R	1.000
X:107840784:C:T	P40L	1.000
X:107840787:T:C	L41P	1.000
X:107840790:T:C	L42P	1.000
X:107840793:T:A	L43H	1.000
X:107840793:T:C	L43P	1.000
X:107840798:T:A	C45S	1.000

dbSNP variants (sampled 300 via entrez): RS1000018310 (X:107832539 C>G,T), RS1000027700 (X:107866439 A>G), RS1000027892 (X:107848506 G>T), RS1000070230 (X:107863130 G>C), RS1000085650 (X:107837145 C>T), RS1000097658 (X:107925924 G>T), RS1000104939 (X:107912636 T>C), RS1000111570 (X:107858768 A>G), RS1000137205 (X:107884778 A>G), RS1000180695 (X:107870186 G>A), RS1000240136 (X:107925190 T>C), RS1000297561 (X:107825797 G>T), RS1000397602 (X:107870820 A>G), RS1000438417 (X:107858304 C>G), RS1000493375 (X:107928550 A>G)

Disease associations

OMIM: gene MIM:300204 | disease phenotypes: MIM:300928

GenCC curated gene-disease

Disease	Classification	Inheritance
non-syndromic X-linked intellectual disability	Supportive	X-linked
intellectual disability, X-linked 101	Limited	Unknown

Mondo (2): intellectual disability, X-linked 101 (MONDO:0010489), non-syndromic X-linked intellectual disability (MONDO:0019181)

Orphanet (1): X-linked non-syndromic intellectual disability (Orphanet:777)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000276	Long face
HP:0000322	Short philtrum
HP:0000400	Macrotia
HP:0000486	Strabismus
HP:0000648	Optic atrophy
HP:0000752	Hyperactivity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001419	X-linked recessive inheritance
HP:0002465	Poor speech
HP:0003593	Infantile onset
HP:0007687	Unilateral ptosis
HP:0030084	Clinodactyly

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Benzo(a)pyrene	affects methylation	2
Nickel	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
ethyl-p-hydroxybenzoate	increases expression	1
beta-lapachone	increases expression	1
ferrous chloride	increases expression	1
monomethylpropion	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	affects expression	1
Vanadates	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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