FICD

Summary

FICD (FIC domain protein adenylyltransferase, HGNC:18416) is a protein-coding gene on chromosome 12q23.3, encoding Protein adenylyltransferase FICD (Q9BVA6). Protein that can both mediate the addition of adenosine 5’-monophosphate (AMP) to specific residues of target proteins (AMPylation), and the removal of the same modification from target proteins (de-AMPylation), depending on the context.

Enables several functions, including AMPylase activity; ATP binding activity; and Hsp70 protein binding activity. Involved in protein adenylylation; regulation of IRE1-mediated unfolded protein response; and response to endoplasmic reticulum stress. Located in endoplasmic reticulum membrane.

Source: NCBI Gene 11153 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spastic paraplegia 92, autosomal recessive (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 87 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_007076

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18416
Approved symbol	FICD
Name	FIC domain protein adenylyltransferase
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	HYPE, HIP13
Ensembl gene	ENSG00000198855
Ensembl biotype	protein_coding
OMIM	620875
Entrez	11153

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000361549, ENST00000546448, ENST00000549641, ENST00000552695, ENST00000552758, ENST00000858247, ENST00000858248, ENST00000858249, ENST00000858250

RefSeq mRNA: 1 — MANE Select: NM_007076 NM_007076

CCDS: CCDS9116

Canonical transcript exons

ENST00000552695 — 3 exons

Exon	Start	End
ENSE00000938057	108516915	108517273
ENSE00002411533	108518400	108521210
ENSE00002416045	108515277	108515361

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 85.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.5983 / max 41.1923, expressed in 1450 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127883	2.5983	1450

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	85.80	gold quality
pancreatic ductal cell	CL:0002079	84.72	gold quality
islet of Langerhans	UBERON:0000006	84.51	gold quality
corpus epididymis	UBERON:0004359	83.64	gold quality
adenohypophysis	UBERON:0002196	82.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.80	gold quality
pituitary gland	UBERON:0000007	81.75	gold quality
body of pancreas	UBERON:0001150	81.75	gold quality
cranial nerve II	UBERON:0000941	81.49	gold quality
pancreas	UBERON:0001264	81.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.15	gold quality
stromal cell of endometrium	CL:0002255	79.47	gold quality
left adrenal gland	UBERON:0001234	78.27	gold quality
left adrenal gland cortex	UBERON:0035825	77.84	gold quality
right adrenal gland	UBERON:0001233	77.79	gold quality
adrenal gland	UBERON:0002369	77.54	gold quality
adrenal cortex	UBERON:0001235	77.24	gold quality
parotid gland	UBERON:0001831	77.05	gold quality
secondary oocyte	CL:0000655	77.03	gold quality
right adrenal gland cortex	UBERON:0035827	76.61	gold quality
cauda epididymis	UBERON:0004360	76.07	gold quality
type B pancreatic cell	CL:0000169	75.86	gold quality
adrenal tissue	UBERON:0018303	75.55	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	75.22	gold quality
right lobe of liver	UBERON:0001114	75.18	gold quality
caput epididymis	UBERON:0004358	75.02	gold quality
ileal mucosa	UBERON:0000331	74.73	gold quality
left testis	UBERON:0004533	74.17	gold quality
granulocyte	CL:0000094	74.10	gold quality
right testis	UBERON:0004534	74.07	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.19
E-GEOD-81547	yes	9.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting FICD, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-6515-5P	97.08	65.48	1219

Literature-anchored findings (GeneRIF, showing 8)

• HYPE is an unfolded protein response regulator. (PMID:25601083)
• We first demonstrate efficient enrichment and fast visualization of potential HYPE substrates in cell lysates by in-gel fluorescence, followed by robust identification via shotgun proteomics on a QExactive mass spectrometer (PMID:26604261)
• The single catalytic domain of FICD can release the attached AMP, restoring functionality to BiP. (PMID:27918543)
• FICD-dependent AMPylation remodelling accelerates differentiation of neural progenitor cells into mature neurons. (PMID:31980631)
• A Fluorescence Polarization-Based High-Throughput Screen to Identify the First Small-Molecule Modulators of the Human Adenylyltransferase HYPE/FICD. (PMID:32992526)
• Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD. (PMID:33893288)
• Investigation of the Detailed AMPylated Reaction Mechanism for the Huntingtin Yeast-Interacting Protein E Enzyme HYPE. (PMID:34209803)
• Structures of a deAMPylation complex rationalise the switch between antagonistic catalytic activities of FICD. (PMID:34408154)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ficd	ENSDARG00000035595
mus_musculus	Ficd	ENSMUSG00000053334
rattus_norvegicus	Ficd	ENSRNOG00000059799
drosophila_melanogaster	Fic	FBGN0263278
caenorhabditis_elegans		WBGENE00014004

Protein

Protein identifiers

Protein adenylyltransferase FICD — Q9BVA6 (reviewed: Q9BVA6)

Alternative names: AMPylator FICD, De-AMPylase FICD, FIC domain-containing protein, Huntingtin yeast partner E, Huntingtin-interacting protein 13, Huntingtin-interacting protein E

All UniProt accessions (4): Q9BVA6, F8VZ74, H0YIR6, J3KP49

UniProt curated annotations — full annotation on UniProt →

Function. Protein that can both mediate the addition of adenosine 5’-monophosphate (AMP) to specific residues of target proteins (AMPylation), and the removal of the same modification from target proteins (de-AMPylation), depending on the context. The side chain of Glu-231 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. Acts as a key regulator of the ERN1/IRE1-mediated unfolded protein response (UPR) by mediating AMPylation or de-AMPylation of HSPA5/BiP. In unstressed cells, acts as an adenylyltransferase by mediating AMPylation of HSPA5/BiP at ‘Thr-518’, thereby inactivating it. In response to endoplasmic reticulum stress, acts as a phosphodiesterase by mediating removal of ATP (de-AMPylation) from HSPA5/BiP at ‘Thr-518’, leading to restore HSPA5/BiP activity. Although it is able to AMPylate RhoA, Rac and Cdc42 Rho GTPases in vitro, Rho GTPases do not constitute physiological substrates.

Subunit / interactions. Homodimer. Interacts with HD.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitous.

Post-translational modifications. Auto-AMPylated in vitro; it is unclear whether auto-AMPylation is relevant in vivo. N-glycosylated; predominantly glycosylated at Asn-275.

Disease relevance. Spastic paraplegia 92, autosomal recessive (SPG92) [MIM:620911] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG92 is an autosomal recessive form characterized by onset of lower limb spasticity and gait abnormalities in the first or second decade of life. Some patients have mild cognitive deficits. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. The side chain of Glu-234 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity. Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-234 binds ATP and competes with ATP-binding at Arg-374, thereby preventing adenylyltransferase activity. In unstressed cells, disengagement of Glu-234 promotes adenylyltransferase activity. Activation dissociates ATP-binding from Glu-234, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain.

Cofactor. Divalent metal cation. Prefers Mn(2+) over Mg(2+).

Domain organisation. The fido domain mediates the adenylyltransferase activity.

Induction. Up-regulated in response to activation of unfolded protein response (UPR).

Similarity. Belongs to the fic family.

RefSeq proteins (1): NP_009007* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003812	Fido	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR036597	Fido-like_dom_sf	Homologous_superfamily
IPR040198	Fido_containing	Family

Pfam: PF02661

Catalyzed reactions (Rhea), 3 shown:

• L-tyrosyl-[protein] + ATP = O-(5’-adenylyl)-L-tyrosyl-[protein] + diphosphate (RHEA:54288)
• L-threonyl-[protein] + ATP = 3-O-(5’-adenylyl)-L-threonyl-[protein] + diphosphate (RHEA:54292)
• 3-O-(5’-adenylyl)-L-threonyl-[protein] + H2O = L-threonyl-[protein] + AMP + H(+) (RHEA:55932)

UniProt features (57 total): helix 18, mutagenesis site 11, binding site 5, turn 4, modified residue 3, strand 3, topological domain 2, glycosylation site 2, repeat 2, chain 1, site 1, transmembrane region 1, sequence variant 1, domain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
7B7Z	X-RAY DIFFRACTION	1.7
7B80	X-RAY DIFFRACTION	1.87
6I7H	X-RAY DIFFRACTION	2.25
6I7L	X-RAY DIFFRACTION	2.32
6I7I	X-RAY DIFFRACTION	2.33
4U04	X-RAY DIFFRACTION	2.48
4U0S	X-RAY DIFFRACTION	2.49
6I7K	X-RAY DIFFRACTION	2.54
9YZ5	X-RAY DIFFRACTION	2.58
4U07	X-RAY DIFFRACTION	2.64
6ZMD	X-RAY DIFFRACTION	2.64
6I7J	X-RAY DIFFRACTION	2.65
6I7G	X-RAY DIFFRACTION	2.7
4U0Z	X-RAY DIFFRACTION	2.95
4U0U	X-RAY DIFFRACTION	2.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BVA6-F1	84.29	0.72

Functional residue map

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

Catalytic / active sites (2): 234 (important for autoinhibition of adenylyltransferase activity); 363

Ligand- & substrate-binding residues (5): 316–319; 367–374; 399–400; 407; 234

Post-translational modifications (3): 79, 80, 183

Glycosylation sites (2): 275, 446

Mutagenesis-validated functional residues (11):

Position	Phenotype
76–77	does not affect auto-ampylation.
79–80	decreased ampylation.
168	does not affect level of auto-ampylation.
170	does not affect level of auto-ampylation.
172	does not affect level of auto-ampylation.
183	decreased ampylation.
234	promotes adenylyltransferase activity.
258	abolishes homodimerization.
275	strongly decreased n-glycosylation. abolished n-glycosylation; when associated with q-446.
363	abolishes adenylyltransferase activity.
446	slightly decreased n-glycosylation. abolished n-glycosylation; when associated with q-275.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 226 (showing top): GOBP_IRE1_MEDIATED_UNFOLDED_PROTEIN_RESPONSE, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_REGULATION_OF_IRE1_MEDIATED_UNFOLDED_PROTEIN_RESPONSE, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, MCAATNNNNNGCG_UNKNOWN, BLALOCK_ALZHEIMERS_DISEASE_UP, MODULE_206, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, ATTCTTT_MIR186, GOBP_NEGATIVE_REGULATION_OF_CATALYTIC_ACTIVITY

GO Biological Process (6): response to unfolded protein (GO:0006986), protein adenylylation (GO:0018117), negative regulation of GTPase activity (GO:0034260), response to endoplasmic reticulum stress (GO:0034976), protein deadenylylation (GO:0044602), regulation of IRE1-mediated unfolded protein response (GO:1903894)

GO Molecular Function (12): ATP binding (GO:0005524), Hsp70 protein binding (GO:0030544), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein adenylylhydrolase activity (GO:0044603), protein-folding chaperone binding (GO:0051087), AMPylase activity (GO:0070733), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), hydrolase activity (GO:0016787)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
catalytic activity	2
response to topologically incorrect protein	1
protein nucleotidylation	1
GTPase activity	1
regulation of GTPase activity	1
negative regulation of biological process	1
negative regulation of hydrolase activity	1
cellular response to stress	1
protein denucleotidylation	1
IRE1-mediated unfolded protein response	1
regulation of endoplasmic reticulum unfolded protein response	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
heat shock protein binding	1
protein-folding chaperone binding	1
identical protein binding	1
protein dimerization activity	1
phosphoric diester hydrolase activity	1
catalytic activity, acting on a protein	1
adenylyltransferase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FICD	PRPF40B	Q6NWY9	833
FICD	HTT	P42858	831
FICD	PRPF40A	O75400	659
FICD	MAGEA3	P43357	601
FICD	ATP8B1	O43520	522
FICD	SETD2	Q9BYW2	436
FICD	GATC	O43716	426
FICD	RIPK4	P57078	401
FICD	C11orf68	Q9H3H3	401
FICD	PTCHD1	Q96NR3	395
FICD	CDC42	P21181	386
FICD	SELENOO	Q9BVL4	375
FICD	HSPA5	P11021	373
FICD	PRODH2	Q9UF12	367
FICD	RAG2	P55895	365

IntAct

16 interactions, top by confidence:

A	B	Type	Score
FICD	FICD	psi-mi:“MI:1148”(ampylation reaction)	0.740
FICD	FICD	psi-mi:“MI:0407”(direct interaction)	0.740
HTT	FICD	psi-mi:“MI:0915”(physical association)	0.560
FICD	CDC42	psi-mi:“MI:1148”(ampylation reaction)	0.440
FICD	RAC1	psi-mi:“MI:1148”(ampylation reaction)	0.440
FICD	ADK	psi-mi:“MI:0915”(physical association)	0.370
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMEM169	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC6A11	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): FICD (Affinity Capture-RNA), FICD (Two-hybrid), FICD (Affinity Capture-MS), FICD (Affinity Capture-MS), FICD (Affinity Capture-MS), RAB14 (Cross-Linking-MS (XL-MS)), FICD (Affinity Capture-MS), FICD (Affinity Capture-RNA), FICD (Two-hybrid), FICD (Two-hybrid)

ESM2 similar proteins: A0A061I403, A7SVT1, A8X181, B0B8S7, B0B970, B0BAF6, B0W429, B3MK83, B3N5J3, B4F6I5, B4GJC1, B4I1V5, B4JBN5, B4KFW6, B4LQT7, B4MUQ2, B4P0E1, B4Q4M7, B7F7B9, D8WUA4, F3YDF1, G7LCC3, O59824, O84707, O88967, P0DPS8, P32795, P39143, P45876, P46508, Q17A75, Q23544, Q29JP8, Q36795, Q3KKZ3, Q3KM61, Q55575, Q6AY47, Q6E0V2, Q6MDI5

Diamond homologs: A0A061I403, A7SVT1, A8X181, B0W429, B3MK83, B3N5J3, B4F6I5, B4GJC1, B4I1V5, B4JBN5, B4KFW6, B4LQT7, B4MUQ2, B4P0E1, B4Q4M7, O66426, Q06277, Q17A75, Q23544, Q29JP8, Q4UWF4, Q54RJ6, Q6AY47, Q6ZM51, Q8BIX9, Q8E9K5, Q8SWV6, Q9BVA6, Q9K0V1, Q5ZXN6, A0A1S4NYE3, A1JU65, B3BM48, O68703, P0C2N1, P15320, P27475, Q0T963, Q3YL96, Q93RN4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	76
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3899938	FICD, ARG374HIS	Pathogenic
3899939	FICD, 2-BP DEL, 1109GG (rs1191700402)	Pathogenic
4822008	NM_007076.3(FICD):c.1121G>A (p.Arg374His)	Likely pathogenic

SpliceAI

965 predictions. Top by Δscore:

Variant	Effect	Δscore
12:108517274:G:C	donor_loss	1.0000
12:108517275:T:A	donor_loss	1.0000
12:108518398:A:AG	acceptor_gain	1.0000
12:108518399:G:GT	acceptor_gain	1.0000
12:108518399:GC:G	acceptor_gain	1.0000
12:108524314:A:AC	donor_gain	1.0000
12:108524314:ACG:A	donor_gain	1.0000
12:108524314:ACGCT:A	donor_gain	1.0000
12:108524315:C:CC	donor_gain	1.0000
12:108524315:CG:C	donor_gain	1.0000
12:108524315:CGC:C	donor_gain	1.0000
12:108524315:CGCT:C	donor_gain	1.0000
12:108524315:CGCTC:C	donor_gain	1.0000
12:108524359:T:TA	donor_gain	1.0000
12:108524386:T:A	donor_gain	1.0000
12:108524502:AGGCC:A	acceptor_gain	1.0000
12:108524503:GGCC:G	acceptor_gain	1.0000
12:108524504:GCC:G	acceptor_gain	1.0000
12:108524505:CC:C	acceptor_gain	1.0000
12:108524505:CCC:C	acceptor_gain	1.0000
12:108524506:CC:C	acceptor_gain	1.0000
12:108524507:C:CC	acceptor_gain	1.0000
12:108524507:C:CG	acceptor_loss	1.0000
12:108524507:C:T	acceptor_gain	1.0000
12:108524508:T:A	acceptor_loss	1.0000
12:108525452:CTGA:C	donor_loss	1.0000
12:108525453:TGAC:T	donor_loss	1.0000
12:108525456:C:CT	donor_loss	1.0000
12:108525607:CAC:C	acceptor_gain	1.0000
12:108525608:AC:A	acceptor_gain	1.0000

AlphaMissense

3000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:108519156:C:A	A353D	0.999
12:108519185:C:G	H363D	0.999
12:108518538:G:A	G147D	0.998
12:108518792:G:C	A232P	0.998
12:108519153:C:A	A352E	0.998
12:108519191:T:C	F365L	0.998
12:108519193:C:A	F365L	0.998
12:108519193:C:G	F365L	0.998
12:108519201:G:A	G368D	0.998
12:108519201:G:T	G368V	0.998
12:108519205:C:A	N369K	0.998
12:108519205:C:G	N369K	0.998
12:108519315:C:A	A406D	0.998
12:108519345:G:C	R416P	0.998
12:108519353:G:C	A419P	0.998
12:108519375:T:C	L426P	0.998
12:108518799:A:T	E234V	0.997
12:108518811:T:C	L238P	0.997
12:108519155:G:C	A353P	0.997
12:108519174:T:C	L359P	0.997
12:108519189:C:A	P364H	0.997
12:108519206:G:T	G370W	0.997
12:108519207:G:A	G370E	0.997
12:108519210:G:T	R371M	0.997
12:108519211:G:C	R371S	0.997
12:108519211:G:T	R371S	0.997
12:108519240:T:C	L381P	0.997
12:108518435:G:C	A113P	0.996
12:108518573:G:C	A159P	0.996
12:108518796:T:A	I233N	0.996

dbSNP variants (sampled 300 via entrez): RS1000962338 (12:108518781 A>ACCAC), RS1001260224 (12:108514346 A>C), RS1001684486 (12:108517802 C>T), RS1001714004 (12:108517505 G>C), RS1002356128 (12:108514149 A>C), RS1002517437 (12:108520530 C>CT), RS1002928987 (12:108515336 G>C,T), RS1003208803 (12:108520766 C>T), RS1003232229 (12:108521343 G>C), RS1003264490 (12:108516759 T>C), RS1003361549 (12:108516267 G>T), RS1003392665 (12:108516084 A>G,T), RS1005372029 (12:108515776 C>T), RS1005406347 (12:108521605 G>A,C,T), RS1005862338 (12:108520934 T>C)

Disease associations

OMIM: gene MIM:620875 | disease phenotypes: MIM:620911

GenCC curated gene-disease

Disease	Classification	Inheritance
spastic paraplegia 92, autosomal recessive	Strong	Autosomal recessive

Mondo (1): spastic paraplegia 92, autosomal recessive (MONDO:0975746)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_839	Obesity-related traits	2.000000e-06
GCST002408_11	Response to methotrexate in juvenile idiopathic arthritis	4.000000e-06
GCST002481_2	Acne (severe)	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
Tobacco Smoke Pollution	increases expression	2
Tunicamycin	increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
ferrous chloride	decreases expression	1
celastrol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
gedunin	increases expression	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
NSC 689534	increases expression, affects binding	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Copper	affects binding, increases expression	1
Drugs, Chinese Herbal	increases expression	1
Estradiol	increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Oils	increases expression	1
Polystyrenes	increases expression	1

Clinical trials (associated diseases)

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