TMEM94

Summary

TMEM94 (transmembrane protein 94, HGNC:28983) is a protein-coding gene on chromosome 17q25.1, encoding Transmembrane protein 94 (Q12767). Could function in the uptake of Mg(2+) from the cytosol into the endoplasmic reticulum and regulate intracellular Mg(2+) homeostasis.

Enables P-type magnesium transporter activity. Involved in magnesium ion transport from cytosol to endoplasmic reticulum. Is active in endoplasmic reticulum membrane.

Source: NCBI Gene 9772 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder with cardiac defects and dysmorphic facies (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 323 total — 10 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 60
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_014738

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28983
Approved symbol	TMEM94
Name	transmembrane protein 94
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	ERMA
Ensembl gene	ENSG00000177728
Ensembl biotype	protein_coding
OMIM	618163
Entrez	9772

Gene structure

Transcript identifiers

Ensembl transcripts: 64 — 44 protein_coding, 15 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000314256, ENST00000375248, ENST00000577194, ENST00000577245, ENST00000577247, ENST00000577380, ENST00000578624, ENST00000578853, ENST00000579241, ENST00000579707, ENST00000579898, ENST00000580416, ENST00000580441, ENST00000580849, ENST00000580918, ENST00000581085, ENST00000581252, ENST00000581453, ENST00000581519, ENST00000581723, ENST00000581834, ENST00000581867, ENST00000582186, ENST00000582455, ENST00000582843, ENST00000583071, ENST00000583296, ENST00000583795, ENST00000584383, ENST00000584694, ENST00000585105, ENST00000585277, ENST00000705117, ENST00000861530, ENST00000861531, ENST00000861532, ENST00000861533, ENST00000861534, ENST00000861535, ENST00000861536, ENST00000861537, ENST00000861538, ENST00000861539, ENST00000861540, ENST00000861541, ENST00000861542, ENST00000861543, ENST00000861544, ENST00000861545, ENST00000861546, ENST00000861547, ENST00000861548, ENST00000861549, ENST00000861550, ENST00000937075, ENST00000937076, ENST00000937077, ENST00000937078, ENST00000937079, ENST00000937080, ENST00000956009, ENST00000956010, ENST00000956011, ENST00000956012

RefSeq mRNA: 5 — MANE Select: NM_014738 NM_001321148, NM_001321149, NM_001351202, NM_001351203, NM_014738

CCDS: CCDS32732, CCDS82204, CCDS92392, CCDS92394

Canonical transcript exons

ENST00000314256 — 32 exons

Exon	Start	End
ENSE00001233085	75493491	75493593
ENSE00001233091	75492929	75493102
ENSE00002694827	75456635	75456751
ENSE00003472421	75495544	75495643
ENSE00003491587	75492474	75492789
ENSE00003495726	75491303	75491455
ENSE00003501989	75495284	75495399
ENSE00003508585	75498444	75498538
ENSE00003510722	75488759	75488910
ENSE00003515940	75489266	75489368
ENSE00003532126	75499262	75500452
ENSE00003535010	75497113	75497198
ENSE00003536335	75471800	75471929
ENSE00003546121	75495966	75496074
ENSE00003557936	75496730	75496807
ENSE00003559751	75498912	75499082
ENSE00003570034	75489576	75489662
ENSE00003570584	75486290	75486426
ENSE00003571919	75498629	75498722
ENSE00003595238	75485428	75485547
ENSE00003604144	75498175	75498323
ENSE00003621204	75485871	75485998
ENSE00003630734	75493699	75493916
ENSE00003632202	75491049	75491153
ENSE00003644547	75490702	75490758
ENSE00003644659	75494896	75495034
ENSE00003657041	75496282	75496471
ENSE00003660521	75491691	75491900
ENSE00003668745	75487932	75488134
ENSE00003684256	75497781	75497862
ENSE00003685553	75494627	75494808
ENSE00003687976	75490234	75490350

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 97.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0270 / max 284.2620, expressed in 1801 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162722	13.6554	1798
162725	0.5110	135
162724	0.3594	147
162721	0.1910	71
162726	0.1280	56
162729	0.0791	24
162728	0.0553	14
162727	0.0295	12
162723	0.0183	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.97	gold quality
cerebellar hemisphere	UBERON:0002245	97.49	gold quality
cerebellar cortex	UBERON:0002129	97.37	gold quality
right frontal lobe	UBERON:0002810	97.33	gold quality
nucleus accumbens	UBERON:0001882	97.31	gold quality
right adrenal gland cortex	UBERON:0035827	97.24	gold quality
putamen	UBERON:0001874	97.14	gold quality
pituitary gland	UBERON:0000007	97.12	gold quality
right adrenal gland	UBERON:0001233	97.11	gold quality
left adrenal gland cortex	UBERON:0035825	96.97	gold quality
sural nerve	UBERON:0015488	96.96	gold quality
cerebellum	UBERON:0002037	96.94	gold quality
left adrenal gland	UBERON:0001234	96.92	gold quality
right uterine tube	UBERON:0001302	96.89	gold quality
caudate nucleus	UBERON:0001873	96.74	gold quality
amygdala	UBERON:0001876	96.65	gold quality
adrenal gland	UBERON:0002369	96.59	gold quality
adenohypophysis	UBERON:0002196	96.57	gold quality
temporal lobe	UBERON:0001871	96.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.49	gold quality
apex of heart	UBERON:0002098	96.43	gold quality
right lobe of thyroid gland	UBERON:0001119	96.32	gold quality
ganglionic eminence	UBERON:0004023	96.32	gold quality
right ovary	UBERON:0002118	95.94	gold quality
thyroid gland	UBERON:0002046	95.92	gold quality
left lobe of thyroid gland	UBERON:0001120	95.91	gold quality
brain	UBERON:0000955	95.85	gold quality
central nervous system	UBERON:0001017	95.81	gold quality
substantia nigra	UBERON:0002038	95.80	gold quality
left ovary	UBERON:0002119	95.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting TMEM94, 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-4262	100.00	73.26	3931
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-433-3P	99.98	69.37	1203
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 2)

• Fetal Anomalies Associated with Novel Pathogenic Variants in TMEM94. (PMID:32825426)
• ERMA (TMEM94) is a P-type ATPase transporter for Mg[2+] uptake in the endoplasmic reticulum. (PMID:38513662)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem94	ENSDARG00000074506
mus_musculus	Tmem94	ENSMUSG00000020747
rattus_norvegicus	Tmem94	ENSRNOG00000004032
drosophila_melanogaster	l(2)k05819	FBGN0022153
caenorhabditis_elegans	D1007.15	WBGENE00017010

Protein

Protein identifiers

Transmembrane protein 94 — Q12767 (reviewed: Q12767)

Alternative names: Endoplasmic reticulum magnesium ATPase

All UniProt accessions (15): Q12767, A0A994J4Z6, J3KRN3, J3KRU7, J3KS76, J3KT63, J3KTL5, J3QLC5, J3QLM7, J3QRT3, J3QRT7, J3QRY7, J3QS17, J3QS24, J3QSG7

UniProt curated annotations — full annotation on UniProt →

Function. Could function in the uptake of Mg(2+) from the cytosol into the endoplasmic reticulum and regulate intracellular Mg(2+) homeostasis.

Subunit / interactions. Forms homooligomers.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed ubiquitously.

Disease relevance. Intellectual developmental disorder with cardiac defects and dysmorphic facies (IDDCDF) [MIM:618316] An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, intellectual disability, congenital heart malformations, and facial dysmorphism. Dysmorphic features include triangular face, deep set eyes, broad nasal root and tip and anteverted nostrils, thick arched eye brows, hypertrichosis, pointed chin, and hypertelorism. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q12767-1	1	yes
Q12767-2	2
Q12767-3	3

RefSeq proteins (5): NP_001308077, NP_001308078, NP_001338131, NP_001338132, NP_055553* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023298	ATPase_P-typ_TM_dom_sf	Homologous_superfamily
IPR039720	TMEM94	Family

UniProt features (49 total): topological domain 11, transmembrane region 10, modified residue 9, mutagenesis site 4, region of interest 2, short sequence motif 2, compositionally biased region 2, glycosylation site 2, splice variant 2, sequence variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9JK3	ELECTRON MICROSCOPY	2.45
9JJN	ELECTRON MICROSCOPY	2.49
9JJK	ELECTRON MICROSCOPY	2.59
9JK4	ELECTRON MICROSCOPY	2.82
9JK5	ELECTRON MICROSCOPY	2.92
9JJO	ELECTRON MICROSCOPY	3.24

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12767-F1	73.28	0.21

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 (9): 221, 225, 444, 445, 454, 513, 518, 798, 941

Glycosylation sites (2): 1202, 1205

Mutagenesis-validated functional residues (4):

Position	Phenotype
417–418	loss of function in magnesium transport.
1132	loss of function in magnesium transport.
1351–1353	loss of function in magnesium transport. increased degradation. no effect on homooligomerization.
1353	no effect on function in magnesium transport.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 284 (showing top): MORF_RAGE, MORF_ATRX, KENNY_CTNNB1_TARGETS_UP, MORF_ESR1, GOBP_MAGNESIUM_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GCM_RING1, NKX62_Q2, FREAC3_01, MORF_PPP5C, MORF_FANCG, OUELLET_CULTURED_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, MORF_RAP1A, MORF_PML, GOBP_MONOATOMIC_ION_HOMEOSTASIS

GO Biological Process (3): intracellular magnesium ion homeostasis (GO:0010961), magnesium ion transport from cytosol to endoplasmic reticulum (GO:0160176), monoatomic ion transport (GO:0006811)

GO Molecular Function (1): P-type magnesium transporter activity (GO:0015444)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
magnesium ion homeostasis	1
intracellular monoatomic cation homeostasis	1
cytosol to endoplasmic reticulum transport	1
magnesium ion transmembrane transport	1
transport	1
magnesium ion transmembrane transporter activity	1
P-type ion transporter activity	1
ATPase-coupled monoatomic cation transmembrane transporter activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM94	TMEM161A	Q9NX61	612
TMEM94	CASKIN2	Q8WXE0	590
TMEM94	TMEM178A	Q8NBL3	551
TMEM94	TMEM88	Q6PEY1	528
TMEM94	TMEM47	Q9BQJ4	480
TMEM94	SLC38A12	Q8NE00	459
TMEM94	UBB	P02248	457
TMEM94	SLC25A42	Q86VD7	448
TMEM94	TMEM97	Q5BJF2	445
TMEM94	KIAA0513	O60268	440
TMEM94	TMEM260	Q9NX78	435
TMEM94	MYPN	Q86TC9	432
TMEM94	CDK5	Q00535	426
TMEM94	COPZ1	P61923	387
TMEM94	PIBF1	Q8WXW3	374

IntAct

36 interactions, top by confidence:

A	B	Type	Score
CDK5	FIBP	psi-mi:“MI:0914”(association)	0.840
FIBP	CDK5	psi-mi:“MI:0914”(association)	0.840
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
CLTC	TMEM94	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM94	HTR2C	psi-mi:“MI:0915”(physical association)	0.370
TMEM94	BUD31	psi-mi:“MI:0915”(physical association)	0.370
TMEM94	GPR35	psi-mi:“MI:0915”(physical association)	0.370
TMEM94	LTB4R2	psi-mi:“MI:0915”(physical association)	0.370
TMEM94	MC4R	psi-mi:“MI:0915”(physical association)	0.370
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	ABCD4	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
TNFRSF10C	SLC22A23	psi-mi:“MI:0914”(association)	0.350
IL13	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
AVPR1B	KLRG2	psi-mi:“MI:0914”(association)	0.350
RXFP1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
KCNMB3	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
MARCHF4	C2CD2L	psi-mi:“MI:0914”(association)	0.350
SLC17A2	ABCD4	psi-mi:“MI:0914”(association)	0.350
LYPD3	TNPO2	psi-mi:“MI:0914”(association)	0.350

BioGRID (54): KIAA0195 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), KIAA0195 (Proximity Label-MS), KIAA0195 (Proximity Label-MS), KIAA0195 (Proximity Label-MS)

ESM2 similar proteins: A4D1U4, A4IJ06, A6QNT4, B5X2S3, D2I1E3, F1M5F3, F1N2W9, F1QDI9, I0IUP4, O88910, O88954, P50747, P52633, P55266, P59679, P97616, Q05AA6, Q09M05, Q0IEG8, Q0PGW2, Q12767, Q13474, Q14164, Q1LZF2, Q2KHI9, Q2YDD2, Q3UHG7, Q496Y0, Q4U2V3, Q5RDA1, Q641K1, Q69ZK0, Q6NTL4, Q6ZT62, Q7ZU92, Q8HXH0, Q8K2I9, Q8NFZ0, Q8R2S9, Q8TCU6

Diamond homologs: Q12767, Q7TSH8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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
Class A/1 (Rhodopsin-like receptors)	5	13.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	9
Uncertain significance	210
Likely benign	52
Benign	5

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1177446	NM_014738.6(TMEM94):c.606dup (p.Ile203fs)	Pathogenic
1177447	NM_014738.6(TMEM94):c.2729-2A>G	Pathogenic
2062831	NM_014738.6(TMEM94):c.1450C>T (p.Gln484Ter)	Pathogenic
2227854	NM_014738.6(TMEM94):c.2215C>T (p.Arg739Ter)	Pathogenic
3458654	NM_014738.6(TMEM94):c.3433dup (p.His1145fs)	Pathogenic
598743	NM_014738.6(TMEM94):c.2605dup (p.Met869fs)	Pathogenic
598744	NM_014738.6(TMEM94):c.765-1G>C	Pathogenic
617671	NM_014738.6(TMEM94):c.3998+5G>A	Pathogenic
817873	NM_014738.6(TMEM94):c.495_496dup (p.His166fs)	Pathogenic
915311	NM_014738.6(TMEM94):c.1600C>T (p.Gln534Ter)	Pathogenic
1180648	NM_014738.6(TMEM94):c.683dup (p.Glu229fs)	Likely pathogenic
3061285	NM_014738.6(TMEM94):c.955-2A>G	Likely pathogenic
3255586	NM_014738.6(TMEM94):c.1176dup (p.Thr393fs)	Likely pathogenic
3367177	NM_014738.6(TMEM94):c.2485_2494del (p.Ser829fs)	Likely pathogenic
3377755	NM_014738.6(TMEM94):c.2845-1G>A	Likely pathogenic
3776390	NM_014738.6(TMEM94):c.1998_1999dup (p.Thr667fs)	Likely pathogenic
3780718	NM_014738.6(TMEM94):c.1491dup (p.Glu498fs)	Likely pathogenic
4279649	NM_014738.6(TMEM94):c.2194A>T (p.Lys732Ter)	Likely pathogenic
617668	NM_014738.6(TMEM94):c.810del (p.Asp270fs)	Likely pathogenic

SpliceAI

6109 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75471799:GAT:G	acceptor_gain	1.0000
17:75485426:A:AG	acceptor_gain	1.0000
17:75485426:AG:A	acceptor_gain	1.0000
17:75485427:G:GG	acceptor_gain	1.0000
17:75485427:GG:G	acceptor_gain	1.0000
17:75485427:GGGC:G	acceptor_gain	1.0000
17:75485520:G:GT	donor_gain	1.0000
17:75485529:G:GT	donor_gain	1.0000
17:75485545:A:T	donor_gain	1.0000
17:75485545:AAGG:A	donor_loss	1.0000
17:75485547:GGT:G	donor_loss	1.0000
17:75485548:G:C	donor_loss	1.0000
17:75485549:T:A	donor_loss	1.0000
17:75485594:G:T	donor_gain	1.0000
17:75486426:GGT:G	donor_loss	1.0000
17:75486427:G:T	donor_loss	1.0000
17:75486428:T:A	donor_loss	1.0000
17:75489263:CAGA:C	acceptor_loss	1.0000
17:75489264:A:AG	acceptor_gain	1.0000
17:75489264:AGAT:A	acceptor_gain	1.0000
17:75489264:AGATG:A	acceptor_gain	1.0000
17:75489265:G:GC	acceptor_gain	1.0000
17:75489265:GA:G	acceptor_gain	1.0000
17:75489265:GAT:G	acceptor_gain	1.0000
17:75489265:GATG:G	acceptor_gain	1.0000
17:75489265:GATGG:G	acceptor_gain	1.0000
17:75489332:G:GG	donor_gain	1.0000
17:75489369:G:GG	donor_gain	1.0000
17:75491298:TGCA:T	acceptor_loss	1.0000
17:75491299:GCAG:G	acceptor_loss	1.0000

AlphaMissense

8883 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75493553:T:A	W717R	1.000
17:75493553:T:C	W717R	1.000
17:75494918:T:C	L871P	1.000
17:75494929:T:A	W875R	1.000
17:75494929:T:C	W875R	1.000
17:75494930:G:C	W875S	1.000
17:75494931:G:C	W875C	1.000
17:75494931:G:T	W875C	1.000
17:75494934:C:A	N876K	1.000
17:75494934:C:G	N876K	1.000
17:75494935:T:C	C877R	1.000
17:75494937:C:G	C877W	1.000
17:75494938:C:G	H878D	1.000
17:75494942:T:A	I879N	1.000
17:75494948:T:C	L881P	1.000
17:75495545:C:A	A949D	1.000
17:75495551:T:A	L951Q	1.000
17:75495551:T:C	L951P	1.000
17:75495554:C:A	P952H	1.000
17:75495580:C:G	H961D	1.000
17:75495584:T:C	L962P	1.000
17:75495596:A:T	D966V	1.000
17:75495602:T:A	V968E	1.000
17:75495605:C:A	P969H	1.000
17:75495608:T:C	L970P	1.000
17:75495611:T:C	L971P	1.000
17:75495620:T:C	L974P	1.000
17:75495623:T:C	F975S	1.000
17:75499285:G:C	R1341P	1.000
17:75499294:T:C	L1344P	1.000

dbSNP variants (sampled 300 via entrez): RS1000015361 (17:75499498 T>C), RS1000128277 (17:75457889 C>T), RS1000135693 (17:75491090 C>T), RS1000145185 (17:75478344 A>G), RS1000240380 (17:75500727 G>A), RS1000296446 (17:75488190 C>T), RS1000428552 (17:75465023 A>G), RS1000487164 (17:75469793 A>G,T), RS1000516421 (17:75470063 A>G), RS1000766914 (17:75476554 G>A), RS1000843011 (17:75456692 G>A), RS1000850538 (17:75499588 G>A), RS1000984604 (17:75477275 G>C), RS1001007324 (17:75463253 A>G), RS1001026613 (17:75489452 C>T)

Disease associations

OMIM: gene MIM:618163 | disease phenotypes: MIM:618316

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with cardiac defects and dysmorphic facies	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
intellectual developmental disorder with cardiac defects and dysmorphic facies	Definitive	AR

Mondo (3): intellectual developmental disorder with cardiac defects and dysmorphic facies (MONDO:0032672), congenital nervous system disorder (MONDO:0002320), prostate cancer (MONDO:0008315)

Orphanet (3): TMEM94-associated congenital heart defect-facial dysmorphism-developmental delay syndrome (Orphanet:562569), Familial prostate cancer (Orphanet:1331), Rare syndromic intellectual disability (Orphanet:102369)

HPO phenotypes

60 total (30 of 60 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000219	Thin upper lip vermilion
HP:0000256	Macrocephaly
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000465	Webbed neck
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000545	Myopia
HP:0000664	Synophrys
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0000998	Hypertrichosis
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001328	Specific learning disability
HP:0001539	Omphalocele
HP:0001629	Ventricular septal defect

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003042_1	Sight-threatening diabetic retinopathy in type 2 diabetes	7.000000e-07
GCST009362_2	HDL cholesterol levels x long total sleep time interaction (1df test)	7.000000e-06
GCST009362_3	HDL cholesterol levels x long total sleep time interaction (1df test)	6.000000e-07
GCST009368_53	HDL cholesterol levels x long total sleep time interaction (2df test)	5.000000e-10
GCST009368_58	HDL cholesterol levels x long total sleep time interaction (2df test)	3.000000e-07
GCST009368_82	HDL cholesterol levels x long total sleep time interaction (2df test)	3.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067295 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.29	Kd	51.31	nM	CHEMBL3752910
7.11	ED50	77.64	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148622: Binding affinity to human KIAA0195 incubated for 45 mins by Kinobead based pull down assay	kd	0.0513	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
Valproic Acid	affects cotreatment, decreases expression, affects expression	3
Acetaminophen	decreases expression	2
Cisplatin	decreases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
chloroacetaldehyde	decreases expression	1
beta-lapachone	increases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Cidofovir	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	increases phosphorylation	1
Clodronic Acid	affects expression	1
Doxorubicin	decreases expression	1
Ifosfamide	decreases expression	1
Oxygen	decreases expression	1
Smoke	decreases expression	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651664	Binding	Binding affinity to human KIAA0195 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer