ATAD1

Summary

ATAD1 (ATPase family AAA domain containing 1, HGNC:25903) is a protein-coding gene on chromosome 10q23.31, encoding Outer mitochondrial transmembrane helix translocase (Q8NBU5). Outer mitochondrial translocase required to remove mislocalized tail-anchored transmembrane proteins on mitochondria.

Predicted to enable ATP hydrolysis activity. Involved in extraction of mislocalized protein from mitochondrial outer membrane. Located in mitochondrial outer membrane and peroxisomal membrane. Implicated in hyperekplexia 4.

Source: NCBI Gene 84896 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyperekplexia 4 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 220 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 39
• MANE Select transcript: NM_001321967

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25903
Approved symbol	ATAD1
Name	ATPase family AAA domain containing 1
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14600, Msp1
Ensembl gene	ENSG00000138138
Ensembl biotype	protein_coding
OMIM	614452
Entrez	84896

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 33 protein_coding, 4 nonsense_mediated_decay

ENST00000308448, ENST00000328142, ENST00000495903, ENST00000680024, ENST00000680388, ENST00000681308, ENST00000681602, ENST00000681629, ENST00000852089, ENST00000852090, ENST00000852091, ENST00000852092, ENST00000852093, ENST00000852094, ENST00000852095, ENST00000852096, ENST00000852097, ENST00000852098, ENST00000852099, ENST00000852100, ENST00000852101, ENST00000852102, ENST00000852103, ENST00000940754, ENST00000940755, ENST00000940756, ENST00000944898, ENST00000944899, ENST00000944900, ENST00000944901, ENST00000944902, ENST00000944903, ENST00000944904, ENST00000944905, ENST00000944906, ENST00000944907, ENST00000944908

RefSeq mRNA: 4 — MANE Select: NM_001321967 NM_001321967, NM_001321968, NM_001321969, NM_032810

CCDS: CCDS7386

Canonical transcript exons

ENST00000680024 — 10 exons

Exon	Start	End
ENSE00000932769	87756789	87756922
ENSE00000932770	87767673	87767723
ENSE00000932771	87770952	87771041
ENSE00000932772	87776321	87776427
ENSE00000998863	87784470	87784670
ENSE00001883546	87751512	87754807
ENSE00003669323	87790310	87790430
ENSE00003683223	87792657	87792755
ENSE00003911556	87814438	87814612
ENSE00003913563	87818167	87818226

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 96.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.8732 / max 488.0229, expressed in 1807 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110442	33.8780	1805
110440	0.5899	189
110441	0.1668	78
110436	0.0588	16
110439	0.0468	30
110438	0.0413	14
110445	0.0394	3
110437	0.0294	10
110444	0.0199	3
110443	0.0030	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	96.65	gold quality
left testis	UBERON:0004533	96.53	gold quality
islet of Langerhans	UBERON:0000006	95.18	gold quality
cortical plate	UBERON:0005343	94.98	gold quality
adrenal tissue	UBERON:0018303	93.56	gold quality
right atrium auricular region	UBERON:0006631	93.14	gold quality
smooth muscle tissue	UBERON:0001135	92.91	gold quality
testis	UBERON:0000473	92.87	gold quality
calcaneal tendon	UBERON:0003701	92.85	gold quality
rectum	UBERON:0001052	92.70	gold quality
ganglionic eminence	UBERON:0004023	92.37	gold quality
ventricular zone	UBERON:0003053	92.23	gold quality
gastrocnemius	UBERON:0001388	92.01	gold quality
cardiac atrium	UBERON:0002081	92.00	gold quality
muscle of leg	UBERON:0001383	91.94	gold quality
stromal cell of endometrium	CL:0002255	91.51	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.38	gold quality
popliteal artery	UBERON:0002250	90.07	gold quality
tibial artery	UBERON:0007610	90.07	gold quality
prefrontal cortex	UBERON:0000451	89.97	gold quality
heart left ventricle	UBERON:0002084	89.82	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.79	gold quality
gall bladder	UBERON:0002110	89.31	gold quality
anterior cingulate cortex	UBERON:0009835	89.24	gold quality
aorta	UBERON:0000947	89.23	gold quality
heart	UBERON:0000948	89.09	gold quality
descending thoracic aorta	UBERON:0002345	89.02	gold quality
cardiac ventricle	UBERON:0002082	89.01	gold quality
vermiform appendix	UBERON:0001154	89.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

147 targeting ATAD1, 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-5193	100.00	67.26	1744
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 9)

• This study showed that the molecular and functional analyses identify an activating ATAD1 mutation as a new cause of severe encephalopathy and congenital stiffness. (PMID:29390050)
• Sorting out how Msp1 maintains mitochondrial membrane proteostasis. (PMID:31394253)
• CircRNA circ-ATAD1 Is Upregulated in Cervical Squamous Cell Carcinoma and Regulates Cell Proliferation and Apoptosis by Suppressing the Maturation of miR-218. (PMID:34254279)
• Circ-ATAD1 is overexpressed in osteosarcoma (OS) and suppresses the maturation of miR-154-5p to increase cell invasion and migration. (PMID:34857012)
• CircRNA circ-ATAD1 suppresses miR-618 maturation to participate in colorectal cancer. (PMID:35505304)
• Collateral deletion of the mitochondrial AAA+ ATPase ATAD1 sensitizes cancer cells to proteasome dysfunction. (PMID:36409067)
• Neonatal Hypertonia and Progressive Respiratory Failure due to Novel Heterozygous Mutation in ATAD1. (PMID:36933275)
• ATAD1 inhibits hepatitis C virus infection by removing the viral TA-protein NS5B from mitochondria. (PMID:37789674)
• ATAD1 prevents clogging of TOM and damage caused by un-imported mitochondrial proteins. (PMID:39024102)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	atad1a	ENSDARG00000023267
danio_rerio	atad1b	ENSDARG00000056609
mus_musculus	Atad1	ENSMUSG00000013662
drosophila_melanogaster	Fign	FBGN0031519
drosophila_melanogaster	kat-60L1	FBGN0037375
drosophila_melanogaster	Kat60	FBGN0040208
caenorhabditis_elegans	mei-1	WBGENE00003183
caenorhabditis_elegans		WBGENE00017981

Paralogs (9): SPAST (ENSG00000021574), KATNAL1 (ENSG00000102781), VPS4B (ENSG00000119541), FIGNL1 (ENSG00000132436), VPS4A (ENSG00000132612), KATNAL2 (ENSG00000167216), FIGN (ENSG00000182263), KATNA1 (ENSG00000186625), FIGNL2 (ENSG00000261308)

Protein

Protein identifiers

Outer mitochondrial transmembrane helix translocase — Q8NBU5 (reviewed: Q8NBU5)

Alternative names: ATPase family AAA domain-containing protein 1, Thorase

All UniProt accessions (6): Q8NBU5, A0A7P0T7Z9, A0A7P0T9B4, A0A7P0T9U2, A0A7P0TAM5, A0A7P0Z4J1

UniProt curated annotations — full annotation on UniProt →

Function. Outer mitochondrial translocase required to remove mislocalized tail-anchored transmembrane proteins on mitochondria. Specifically recognizes and binds tail-anchored transmembrane proteins: acts as a dislocase that mediates the ATP-dependent extraction of mistargeted tail-anchored transmembrane proteins from the mitochondrion outer membrane. Also plays a critical role in regulating the surface expression of AMPA receptors (AMPAR), thereby regulating synaptic plasticity and learning and memory. Required for NMDA-stimulated AMPAR internalization and inhibition of GRIA1 and GRIA2 recycling back to the plasma membrane; these activities are ATPase-dependent.

Subunit / interactions. Interacts with GRIA2 and GRIP1 in an ATP-dependent manner. ATAD1-catalyzed ATP hydrolysis disrupts not only its binding to GRIA2 and GRIP1, but also interaction between GRIP1 and GRIA2, leading to AMPAR complex disassembly.

Subcellular location. Mitochondrion outer membrane. Peroxisome membrane. Postsynaptic cell membrane.

Disease relevance. Hyperekplexia 4 (HKPX4) [MIM:618011] An autosomal recessive severe neurologic disorder apparent from birth. HKPX4 is characterized by little if any development, hypertonia, early-onset refractory seizures in some patients, and respiratory failure resulting in early death, mostly in the first months of life. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the AAA ATPase family. MSP1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NBU5-1	1	yes
Q8NBU5-2	2

RefSeq proteins (4): NP_001308896, NP_001308897, NP_001308898, NP_116199 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR003960	ATPase_AAA_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041569	AAA_lid_3	Domain
IPR051701	Mito_OM_Translocase_MSP1	Family

Pfam: PF00004, PF17862

Catalyzed reactions (Rhea), 1 shown:

• [protein]-with a C-terminal TM segment(out) + ATP + H2O = [protein]-with a C-terminal TM segment(in) + ADP + phosphate + H(+) (RHEA:66168)

UniProt features (40 total): helix 18, strand 9, sequence variant 3, topological domain 2, turn 2, chain 1, sequence conflict 1, transmembrane region 1, binding site 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7UPR	ELECTRON MICROSCOPY	3.2
7UPT	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBU5-F1	84.05	0.45

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 (1): 133–140

Post-translational modifications (1): 322

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9603798	Class I peroxisomal membrane protein import
R-HSA-9609507	Protein localization

MSigDB gene sets: 267 (showing top): GOBP_MEMORY, GOBP_COGNITION, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_BEHAVIOR, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RECEPTOR_MEDIATED_ENDOCYTOSIS, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_RECEPTOR_INTERNALIZATION, WANG_LMO4_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION, GOBP_REGULATION_OF_RECEPTOR_MEDIATED_ENDOCYTOSIS, GOBP_LEARNING

GO Biological Process (6): positive regulation of receptor internalization (GO:0002092), learning (GO:0007612), memory (GO:0007613), negative regulation of synaptic transmission, glutamatergic (GO:0051967), regulation of postsynaptic neurotransmitter receptor internalization (GO:0099149), extraction of mislocalized protein from mitochondrial outer membrane (GO:0140570)

GO Molecular Function (4): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), membrane protein dislocase activity (GO:0140567), nucleotide binding (GO:0000166)

GO Cellular Component (11): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), membrane (GO:0016020), postsynaptic membrane (GO:0045211), glutamatergic synapse (GO:0098978), peroxisome (GO:0005777), plasma membrane (GO:0005886), synapse (GO:0045202), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of receptor internalization	2
learning or memory	2
ATP-dependent activity	2
cytoplasm	2
synapse	2
receptor internalization	1
positive regulation of receptor-mediated endocytosis	1
synaptic transmission, glutamatergic	1
negative regulation of synaptic transmission	1
regulation of synaptic transmission, glutamatergic	1
regulation of biological quality	1
postsynaptic neurotransmitter receptor internalization	1
extraction of mislocalized protein from membrane	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
protein carrier activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
peroxisome	1
microbody membrane	1
synaptic membrane	1
postsynapse	1
microbody	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

2871 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATAD1	GYPA	P02724	884
ATAD1	OPA1	O60313	804
ATAD1	ERV3-1	Q14264	797
ATAD1	ERVFRD-1	P60508	796
ATAD1	CYP1A1	P04798	768
ATAD1	ERVW-1	Q9UQF0	738
ATAD1	TOMM70	O94826	705
ATAD1	DNAJC5	Q9H3Z4	652
ATAD1	ANKZF1	Q9H8Y5	649
ATAD1	SLC4A9	Q96Q91	648
ATAD1	SLC4A1	P02730	643
ATAD1	AKR1C2	P52895	609
ATAD1	GSTM1	P09488	602
ATAD1	EGF	P01133	578
ATAD1	DHFR	P00374	572

IntAct

94 interactions, top by confidence:

A	B	Type	Score
NFKB1	IKBKB	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FAF2	UBB	psi-mi:“MI:0914”(association)	0.640
RELA	NFKBIE	psi-mi:“MI:0914”(association)	0.620
VDAC1	HK1	psi-mi:“MI:0914”(association)	0.560
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
ATAD1	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
ATAD1	TPM2	psi-mi:“MI:0915”(physical association)	0.400
ATAD1	PRMT8	psi-mi:“MI:0915”(physical association)	0.400
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
ATAD1	GOSR1	psi-mi:“MI:0915”(physical association)	0.400
Bmpr1a	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Rab5c		psi-mi:“MI:0914”(association)	0.350
Rmdn3	DERL1	psi-mi:“MI:0914”(association)	0.350
Tmed2		psi-mi:“MI:0914”(association)	0.350
VAPA		psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
COQ8B	TIMM44	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350

BioGRID (134): ATAD1 (Affinity Capture-MS), ATAD1 (Affinity Capture-MS), ATAD1 (Affinity Capture-MS), GOSR1 (Affinity Capture-Western), ATAD1 (Synthetic Growth Defect), ATAD1 (Affinity Capture-MS), ATAD1 (Affinity Capture-MS), ATAD1 (Affinity Capture-MS), ATAD1 (Affinity Capture-MS), ATAD1 (Affinity Capture-MS), ATAD1 (Affinity Capture-MS), ATAD1 (Affinity Capture-MS), ATAD1 (Affinity Capture-MS), TPM2 (Affinity Capture-MS), ATAD1 (Affinity Capture-MS)

ESM2 similar proteins: B4F6J6, D0FH76, F6QV99, O75351, P03974, P18708, P23787, P28737, P46459, P46460, P46461, P46462, P46467, P52917, P54351, P54609, P54774, P54811, P54812, P54815, P55072, Q01853, Q09803, Q0DGP6, Q0VD48, Q3ZBT1, Q503W7, Q505J9, Q54PT2, Q5AG40, Q5R410, Q5R658, Q6GL04, Q75JI3, Q793F9, Q7KN62, Q7ZU99, Q7ZZ25, Q8NBU5, Q8VEJ9

Diamond homologs: A0A8I6AGW3, A0LR74, A2VDN5, A4IHT0, A6NMB9, B2RYN7, B3M301, B3P8A3, B4F6J6, B4G437, B4HGG6, B4JII0, B4K799, B4M0H8, B4NBP4, B4PL32, B4QSF0, B7PXE3, D0FH76, D2VS83, E9QEA3, F4JEX5, F6QV99, J3QK54, O05209, O14114, O14325, O15381, O16299, O28972, O57940, O60058, P03974, P23787, P25694, P32794, P36966, P40340, P46462, P54609

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 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
Activation of NF-kappaB in B cells	5	12.9×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to reactive oxygen species	5	21.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	95
Likely benign	109
Benign	3

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2422866	NC_000010.10:g.(?89514444)(90537999_?)del	Pathogenic
2573834	NM_001321967.2(ATAD1):c.690+1G>C	Pathogenic
688590	GRCh37/hg19 10q23.2-23.31(chr10:89492635-89531333)x1	Pathogenic
3338448	GRCh37/hg19 10q23.31(chr10:89549991-89550223)x0	Likely pathogenic

SpliceAI

2944 predictions. Top by Δscore:

Variant	Effect	Δscore
10:87754730:T:TA	donor_gain	1.0000
10:87756784:CATA:C	donor_loss	1.0000
10:87756785:ATAC:A	donor_loss	1.0000
10:87756786:TA:T	donor_loss	1.0000
10:87756787:A:AC	donor_gain	1.0000
10:87756787:A:C	donor_loss	1.0000
10:87756788:C:CC	donor_gain	1.0000
10:87756788:CCTTT:C	donor_gain	1.0000
10:87756919:CCAC:C	acceptor_gain	1.0000
10:87756920:CACC:C	acceptor_gain	1.0000
10:87756923:C:CA	acceptor_loss	1.0000
10:87756924:T:C	acceptor_gain	1.0000
10:87767671:A:AC	donor_gain	1.0000
10:87767672:C:CC	donor_gain	1.0000
10:87770921:A:C	donor_gain	1.0000
10:87770950:A:AC	donor_gain	1.0000
10:87770951:C:CC	donor_gain	1.0000
10:87770951:CAGG:C	donor_gain	1.0000
10:87784464:GCATA:G	donor_loss	1.0000
10:87784465:CATA:C	donor_loss	1.0000
10:87784466:ATAC:A	donor_loss	1.0000
10:87784467:TAC:T	donor_loss	1.0000
10:87784472:A:AC	donor_gain	1.0000
10:87792651:ACAT:A	donor_loss	1.0000
10:87792654:TAC:T	donor_loss	1.0000
10:87792655:A:AC	donor_gain	1.0000
10:87792655:ACATG:A	donor_gain	1.0000
10:87792656:C:CT	donor_gain	1.0000
10:87792656:CA:C	donor_gain	1.0000
10:87792656:CAT:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000056315 (10:87832529 G>C), RS1000088095 (10:87807908 C>T), RS1000091820 (10:87840086 T>G), RS1000104125 (10:87790108 G>A,T), RS1000115990 (10:87799312 A>G,T), RS1000133471 (10:87795762 G>A,C,T), RS1000147440 (10:87812532 G>A), RS1000181064 (10:87768874 A>T), RS1000246785 (10:87781667 G>A,T), RS1000257741 (10:87751234 C>A,T), RS1000314013 (10:87832286 T>C,G), RS1000317466 (10:87759024 G>GT), RS1000348666 (10:87758662 C>T), RS1000368992 (10:87802250 C>T), RS1000384860 (10:87775352 C>T)

Disease associations

OMIM: gene MIM:614452 | disease phenotypes: MIM:618011

GenCC curated gene-disease

Disease	Classification	Inheritance
hyperekplexia 4	Strong	Autosomal recessive
hereditary hyperekplexia	Supportive	Autosomal dominant

Mondo (3): hyperekplexia 4 (MONDO:0044330), PTEN hamartoma tumor syndrome (MONDO:0017623), hereditary hyperekplexia (MONDO:0021022)

Orphanet (1): PTEN hamartoma tumor syndrome (Orphanet:306498)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000218	High palate
HP:0001181	Adducted thumb
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001298	Encephalopathy
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0001371	Flexion contracture
HP:0001373	Joint dislocation
HP:0001387	Joint stiffness
HP:0001537	Umbilical hernia
HP:0001762	Talipes equinovarus
HP:0002020	Gastroesophageal reflux
HP:0002036	Hiatus hernia
HP:0002059	Cerebral atrophy
HP:0002063	Rigidity
HP:0002360	Sleep disturbance
HP:0002380	Fasciculations
HP:0002521	Hypsarrhythmia
HP:0002751	Kyphoscoliosis
HP:0002827	Hip dislocation
HP:0002878	Respiratory failure
HP:0003552	Muscle stiffness

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006288_110	Heel bone mineral density	4.000000e-07
GCST006288_637	Heel bone mineral density	1.000000e-10
GCST012227_614	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects expression, increases abundance	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
aflatoxin B2	decreases methylation	1
coumarin	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	increases expression	1
Caffeine	decreases phosphorylation	1
Coal	increases abundance, decreases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1
Smoke	decreases expression, increases abundance	1
Testosterone	decreases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SD78	HAP1 ATAD1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04094675	PHASE2	COMPLETED	Sirolimus for Cowden Syndrome With Colon Polyposis
NCT01476514	Not specified	TERMINATED	Effects of Mutations of the Glycine Gene Associated With Hyperekplexia on Central Pain Processing
NCT05168969	Not specified	COMPLETED	Hyperekplexia in Patients With CTNNB1 Mutation
NCT05652101	Not specified	RECRUITING	Hyperekplexia : Adaptative Skills and Neurodevelopmental Trajectory
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT07218575	PHASE2/PHASE3	NOT_YET_RECRUITING	Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations
NCT02991807	PHASE1/PHASE2	COMPLETED	RAD001 and Neurocognition in PTEN Hamartoma Tumor Syndrome
NCT06080165	PHASE1/PHASE2	WITHDRAWN	Sirolimus for Improving Social Abilities in People With PTEN Germline Mutations
NCT02461446	Not specified	RECRUITING	Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03630523	Not specified	UNKNOWN	Response of Immune System to Flu Vaccination in PHTS
NCT05671107	Not specified	COMPLETED	Development and Validation of an Online Neurobehavioral Evaluation Tool for PTEN Patients
NCT06462430	Not specified	RECRUITING	PTEN Hamartoma Tumor Syndrome Pediatric Patient Registry