ARL6IP1

Summary

ARL6IP1 (ARL6 interacting reticulophagy regulator 1, HGNC:697) is a protein-coding gene on chromosome 16p12.3, encoding ADP-ribosylation factor-like protein 6-interacting protein 1 (Q15041). Positively regulates SLC1A1/EAAC1-mediated glutamate transport by increasing its affinity for glutamate in a PKC activity-dependent manner.

This gene belongs to the ARL6ip family and encodes a transmembrane protein that is predominantly localized to intracytoplasmic membranes. It is highly expressed in early myeloid progenitor cells and thought to be involved in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation. Mutations in this gene are associated with spastic paraplegia 61 (SPG61). Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 23204 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary spastic paraplegia (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 110 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 15
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_015161

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:697
Approved symbol	ARL6IP1
Name	ARL6 interacting reticulophagy regulator 1
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	AIP1, ARMER, KIAA0069, SPG61
Ensembl gene	ENSG00000170540
Ensembl biotype	protein_coding
OMIM	607669
Entrez	23204

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000304414, ENST00000546206, ENST00000562234, ENST00000562819, ENST00000563861, ENST00000566391, ENST00000567969, ENST00000569976, ENST00000863231, ENST00000863232, ENST00000915469, ENST00000915470

RefSeq mRNA: 2 — MANE Select: NM_015161 NM_001313858, NM_015161

CCDS: CCDS10572, CCDS81951

Canonical transcript exons

ENST00000304414 — 6 exons

Exon	Start	End
ENSE00001315299	18791669	18793370
ENSE00002595404	18801431	18801549
ENSE00003461808	18795464	18795581
ENSE00003527407	18797925	18798044
ENSE00003583207	18794599	18794683
ENSE00003669872	18798701	18798834

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 99.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 114.6957 / max 1684.1445, expressed in 1826 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156566	114.6957	1826

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	99.66	gold quality
ventricular zone	UBERON:0003053	99.65	gold quality
retina	UBERON:0000966	99.63	gold quality
superior frontal gyrus	UBERON:0002661	99.35	gold quality
embryo	UBERON:0000922	99.34	gold quality
ganglionic eminence	UBERON:0004023	99.33	gold quality
postcentral gyrus	UBERON:0002581	99.31	gold quality
cortical plate	UBERON:0005343	99.30	gold quality
pons	UBERON:0000988	99.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.27	gold quality
parietal lobe	UBERON:0001872	99.24	gold quality
orbitofrontal cortex	UBERON:0004167	99.20	gold quality
prefrontal cortex	UBERON:0000451	99.18	gold quality
superior vestibular nucleus	UBERON:0007227	99.15	gold quality
cingulate cortex	UBERON:0003027	99.13	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.13	gold quality
neocortex	UBERON:0001950	99.12	gold quality
cerebral cortex	UBERON:0000956	99.11	gold quality
frontal cortex	UBERON:0001870	99.11	gold quality
frontal lobe	UBERON:0016525	99.11	gold quality
amygdala	UBERON:0001876	99.10	gold quality
anterior cingulate cortex	UBERON:0009835	99.10	gold quality
CA1 field of hippocampus	UBERON:0003881	99.09	gold quality
cerebellar vermis	UBERON:0004720	99.07	gold quality
medial globus pallidus	UBERON:0002477	99.06	gold quality
telencephalon	UBERON:0001893	99.04	gold quality
adrenal tissue	UBERON:0018303	99.04	gold quality
Ammon’s horn	UBERON:0001954	99.02	gold quality
substantia nigra pars compacta	UBERON:0001965	99.00	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	6164.45
E-MTAB-10485	yes	3333.03
E-GEOD-114530	yes	2698.05
E-CURD-112	yes	2676.63
E-HCAD-56	yes	2521.80
E-HCAD-10	yes	2213.08
E-MTAB-8410	yes	2130.41
E-HCAD-24	yes	1233.94
E-MTAB-8530	yes	1115.96
E-MTAB-8559	yes	1094.91
E-GEOD-125970	yes	953.96
E-MTAB-8271	yes	920.05
E-MTAB-8205	yes	527.45
E-HCAD-35	yes	42.19
E-GEOD-134144	yes	31.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting ARL6IP1, 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-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-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-5582-3P	99.86	72.48	4221

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 5)

• novel endoplasmic reticulum integral membrane protein which protects cells by inhibiting caspase-9 activity and reveal a possible role for ARMER in cell survival (PMID:12754298)
• Down-regulation of ARL6IP1 expression arrested CaSki cell cycling at the G0/G1 phase and mitigated CaSki cell migration, determined by wound healing assays. (PMID:20213509)
• ARL6IP1 may play a key role in cisplatin-induced apoptosis in CaSki cervical cancer cells by regulating the expression of apoptosis-associated proteins. (PMID:20372863)
• ARL6ip1 is a three-spanning transmembrane protein with a conophylline binding pocket. (PMID:24076029)
• Mutations in ARL6IP1, which encodes a tetraspan membrane protein localized to the endoplasmic reticulum (ER), have been recently described in a large family with a complicated form of hereditary spastic paraplegia (HSP). Phenotype associated with ARL6IP1 variants may be broader and more acute than so far reported and identifies fatal HSP as the severe end of the phenotypic spectrum of ARL6IP1 variants. (PMID:31272422)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	arl6ip1	ENSDARG00000054578
mus_musculus	Arl6ip1	ENSMUSG00000030654
rattus_norvegicus	Arl6ip1	ENSRNOG00000017751
drosophila_melanogaster	Arl6IP1	FBGN0038453

Protein

Protein identifiers

ADP-ribosylation factor-like protein 6-interacting protein 1 — Q15041 (reviewed: Q15041)

Alternative names: Apoptotic regulator in the membrane of the endoplasmic reticulum

All UniProt accessions (4): Q15041, H3BPJ2, H3BS91, H3BTX6

UniProt curated annotations — full annotation on UniProt →

Function. Positively regulates SLC1A1/EAAC1-mediated glutamate transport by increasing its affinity for glutamate in a PKC activity-dependent manner. Promotes the catalytic efficiency of SLC1A1/EAAC1 probably by reducing its interaction with ARL6IP5, a negative regulator of SLC1A1/EAAC1-mediated glutamate transport. Plays a role in the formation and stabilization of endoplasmic reticulum tubules. Negatively regulates apoptosis, possibly by modulating the activity of caspase-9 (CASP9). Inhibits cleavage of CASP9-dependent substrates and downstream markers of apoptosis but not CASP9 itself. May be involved in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation.

Subunit / interactions. Homooligomer. Heterodimer with ARL6IP5. Interacts with ARL6. Interacts with TMEM33. Interacts with ATL1.

Subcellular location. Endomembrane system. Endoplasmic reticulum membrane. Endoplasmic reticulum.

Tissue specificity. Expressed in all hematopoietic cell lineages, but the highest level of expression is found in early myeloid progenitor cells. Expressed in brain, bone marrow, thymus and lung. Expressed at low level in liver, kidney and spleen. Not detected in heart.

Disease relevance. Spastic paraplegia 61, autosomal recessive (SPG61) [MIM:615685] A complicated form of spastic paraplegia with polysensory and motor neuropathy. Spastic paraplegia is 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The transmembrane domains are required for its ability to shape the endoplasmic reticulum membrane into tubules.

Induction. Down-regulated by apoptotic stimuli.

Similarity. Belongs to the ARL6ip family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15041-1	1	yes
Q15041-2	2
Q15041-3	3

RefSeq proteins (2): NP_001300787, NP_055976* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR052114	ER_autophagy_membrane_reg	Family
IPR057282	RETREG1-3-like_RHD	Domain

Pfam: PF24456

UniProt features (12 total): topological domain 4, transmembrane region 3, splice variant 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15041-F1	84.78	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 315 (showing top): AGGAAGC_MIR5163P, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, RORA1_01, GOBP_PROTEIN_TARGETING, MORF_CDK2, HSIAO_HOUSEKEEPING_GENES, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, MCAATNNNNNGCG_UNKNOWN, FISCHER_G2_M_CELL_CYCLE, GROSS_HYPOXIA_VIA_ELK3_UP, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS

GO Biological Process (7): positive regulation of L-glutamate import across plasma membrane (GO:0002038), cotranslational protein targeting to membrane (GO:0006613), apoptotic process (GO:0006915), negative regulation of apoptotic process (GO:0043066), endoplasmic reticulum tubular network formation (GO:0071787), regulation of endoplasmic reticulum tubular network organization (GO:1903371), endoplasmic reticulum tubular network membrane organization (GO:1990809)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (8): endoplasmic reticulum (GO:0005783), Sec61 translocon complex (GO:0005784), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), endoplasmic reticulum tubular network (GO:0071782), cytoplasm (GO:0005737), endomembrane system (GO:0012505)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
endoplasmic reticulum tubular network organization	3
cytoplasm	2
endoplasmic reticulum subcompartment	2
regulation of L-glutamate import across plasma membrane	1
positive regulation of organic acid transport	1
positive regulation of transmembrane transport	1
positive regulation of amino acid transport	1
L-glutamate import across plasma membrane	1
protein targeting to membrane	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cellular component assembly	1
regulation of organelle organization	1
endoplasmic reticulum membrane organization	1
protein binding	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
translocon complex	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

3339 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARL6IP1	ATL1	Q8WXF7	752
ARL6IP1	ATL3	Q6DD88	734
ARL6IP1	ATL2	Q8NHH9	701
ARL6IP1	REEP2	Q9BRK0	614
ARL6IP1	REEP1	Q9H902	611
ARL6IP1	RTN2	O75298	587
ARL6IP1	RAB3GAP2	Q9H2M9	537
ARL6IP1	SPAST	Q9UBP0	504
ARL6IP1	ARL6IP5	O75915	503
ARL6IP1	PGAP1	Q75T13	499
ARL6IP1	ZFYVE27	Q5T4F4	483
ARL6IP1	ARL6	Q9H0F7	483
ARL6IP1	AP5Z1	O43299	475
ARL6IP1	TOR1AIP1	Q5JTV8	465
ARL6IP1	C19orf12	Q9NSK7	449

IntAct

339 interactions, top by confidence:

A	B	Type	Score
ARL6IP1	ACSF2	psi-mi:“MI:0915”(physical association)	0.830
ARL6IP1	DIABLO	psi-mi:“MI:0915”(physical association)	0.810
DIABLO	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.810
ARL6IP1	RETREG3	psi-mi:“MI:0915”(physical association)	0.780
RETREG3	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.780
CERT1	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.740
ARL6IP1	CERT1	psi-mi:“MI:0915”(physical association)	0.740
ARL6IP1	INPP5K	psi-mi:“MI:0915”(physical association)	0.740
ARL6IP1	SHMT2	psi-mi:“MI:0915”(physical association)	0.720
ARL6IP1	GAD2	psi-mi:“MI:0915”(physical association)	0.720
ARL6IP1	MYG1	psi-mi:“MI:0915”(physical association)	0.720
ZFYVE21	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.720
SPG21	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.720
SNX11	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.720
ARL6IP1	SNX10	psi-mi:“MI:0915”(physical association)	0.720
SHMT2	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.720
GAD2	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.720
MYG1	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (187): ARL6IP1 (Two-hybrid), ARL6IP1 (Two-hybrid), ARL6IP1 (Two-hybrid), ARL6IP1 (Two-hybrid), ARL6IP1 (Two-hybrid), ARL6IP1 (Two-hybrid), ARL6IP1 (Two-hybrid), ARL6IP1 (Two-hybrid), ARL6IP1 (Two-hybrid), ARL6IP1 (Two-hybrid), ARL6IP1 (Two-hybrid), ARL6IP1 (Two-hybrid), GORASP2 (Two-hybrid), WIPI2 (Two-hybrid), SNX10 (Two-hybrid)

ESM2 similar proteins: B0S4Q1, B9EN89, O43462, O54862, O75915, Q0III2, Q0IIK4, Q15041, Q1LZE6, Q28H54, Q3SWT5, Q4G019, Q4KLV1, Q4R4R4, Q502G2, Q56P28, Q5BJC1, Q5E978, Q5E9M1, Q5NV96, Q5R454, Q5R4X8, Q5RAC8, Q5ZLL0, Q66H21, Q66J05, Q66J44, Q68EQ9, Q6AXM5, Q6DFT6, Q6GPZ5, Q6IFY7, Q6INE8, Q7ZYQ3, Q80TA1, Q8BGS7, Q8C025, Q8CHX6, Q8LEQ4, Q8NFR3

Diamond homologs: Q15041, Q5R454, Q9JKW0, Q9VES1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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.

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein transport	9	10.8×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	40
Likely benign	34
Benign	23

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
3024197	NM_015161.3(ARL6IP1):c.112C>T (p.Arg38Ter)	Pathogenic
3024198	NM_015161.3(ARL6IP1):c.92T>C (p.Leu31Pro)	Pathogenic
4809175	NM_015161.3(ARL6IP1):c.198_202del (p.Leu67fs)	Pathogenic
620202	NM_015161.3(ARL6IP1):c.346C>T (p.Arg116Ter)	Pathogenic
101079	NM_015161.3(ARL6IP1):c.577_580del (p.Lys193fs)	Likely pathogenic
474862	NM_015161.3(ARL6IP1):c.409-2A>G	Likely pathogenic
4813361	NM_015161.3(ARL6IP1):c.407_409-197del	Likely pathogenic

SpliceAI

741 predictions. Top by Δscore:

Variant	Effect	Δscore
16:18793162:T:TA	donor_gain	1.0000
16:18793372:T:C	acceptor_gain	1.0000
16:18794679:AAGTA:A	acceptor_gain	1.0000
16:18794680:AGTA:A	acceptor_gain	1.0000
16:18794681:GTA:G	acceptor_gain	1.0000
16:18794681:GTAC:G	acceptor_loss	1.0000
16:18794682:TA:T	acceptor_gain	1.0000
16:18794682:TACTA:T	acceptor_loss	1.0000
16:18794683:ACTAG:A	acceptor_loss	1.0000
16:18794684:C:CC	acceptor_gain	1.0000
16:18794684:C:T	acceptor_loss	1.0000
16:18794685:T:G	acceptor_loss	1.0000
16:18794688:CAA:C	acceptor_gain	1.0000
16:18794689:A:T	acceptor_gain	1.0000
16:18794690:A:AC	acceptor_gain	1.0000
16:18794690:A:C	acceptor_gain	1.0000
16:18795459:AGTAC:A	donor_loss	1.0000
16:18795460:GTACC:G	donor_loss	1.0000
16:18795462:ACC:A	donor_loss	1.0000
16:18795463:C:CA	donor_loss	1.0000
16:18795463:C:CG	donor_loss	1.0000
16:18795463:CCAT:C	donor_gain	1.0000
16:18795471:G:C	donor_gain	1.0000
16:18795480:T:TA	donor_gain	1.0000
16:18795481:C:A	donor_gain	1.0000
16:18797920:CCTA:C	donor_loss	1.0000
16:18797921:CTACC:C	donor_loss	1.0000
16:18798699:A:AC	donor_gain	1.0000
16:18798700:C:CC	donor_gain	1.0000
16:18801426:CTCA:C	donor_loss	1.0000

AlphaMissense

1320 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:18797926:A:G	W97R	0.993
16:18797926:A:T	W97R	0.993
16:18798756:A:G	W39R	0.993
16:18798756:A:T	W39R	0.993
16:18795482:C:A	K130N	0.992
16:18795482:C:G	K130N	0.992
16:18797964:A:T	V84D	0.991
16:18798795:A:G	W26R	0.990
16:18798795:A:T	W26R	0.990
16:18794646:G:T	A149D	0.987
16:18795545:G:C	C109W	0.987
16:18795546:C:T	C109Y	0.987
16:18794638:C:G	G152R	0.986
16:18794638:C:T	G152R	0.986
16:18798754:C:A	W39C	0.986
16:18798754:C:G	W39C	0.986
16:18797994:A:T	V74D	0.985
16:18798703:A:C	F56L	0.984
16:18798703:A:T	F56L	0.984
16:18798705:A:G	F56L	0.984
16:18794637:C:T	G152E	0.983
16:18795537:A:G	L112P	0.982
16:18795547:A:G	C109R	0.982
16:18797976:G:T	A80D	0.982
16:18794621:G:C	N157K	0.981
16:18794621:G:T	N157K	0.981
16:18793346:C:T	G173E	0.980
16:18798018:A:T	V66D	0.978
16:18793343:A:G	L174P	0.977
16:18794613:A:T	L160H	0.977

dbSNP variants (sampled 300 via entrez): RS1000283660 (16:18795904 C>A), RS1000358586 (16:18795657 G>A,C), RS1000626043 (16:18797262 G>A), RS1000658617 (16:18797112 G>T), RS1000841078 (16:18802397 G>C,T), RS1001022854 (16:18791364 C>T), RS1001214129 (16:18803238 A>C), RS1001361241 (16:18793036 C>T), RS1001543398 (16:18797951 C>T), RS1001636053 (16:18801724 G>A,C), RS1001741087 (16:18799838 G>A), RS1002117592 (16:18801572 T>C,G), RS1002243893 (16:18796649 T>C), RS1002425186 (16:18802969 G>A,T), RS1002662055 (16:18800267 C>A)

Disease associations

OMIM: gene MIM:607669 | disease phenotypes: MIM:615685

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spastic paraplegia 61	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
hereditary spastic paraplegia	Definitive	AR

Mondo (1): hereditary spastic paraplegia 61 (MONDO:0014304)

Orphanet (1): Autosomal recessive spastic paraplegia type 61 (Orphanet:401780)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000763	Sensory neuropathy
HP:0001249	Intellectual disability
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001271	Polyneuropathy
HP:0001288	Gait disturbance
HP:0002540	Inability to walk
HP:0002815	Abnormality of the knee
HP:0003438	Absent Achilles reflex
HP:0005109	Abnormal Achilles tendon morphology
HP:0007083	Hyperactive patellar reflex
HP:0007178	Motor polyneuropathy
HP:0011463	Childhood onset
HP:0012407	Scissor gait

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010002_110	Refractive error	9.000000e-10
GCST011126_24	Caffeine consumption from coffee or tea	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, affects cotreatment	4
bisphenol A	affects expression, decreases expression	2
Acetaminophen	increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Valproic Acid	affects expression, increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
dicrotophos	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
sulindac sulfide	decreases expression	1
ferrous chloride	increases expression	1
diallyl trisulfide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	decreases expression	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Arbutin	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	increases expression	1
Cisplatin	decreases expression	1
Demecolcine	decreases expression	1
Dimethyl Sulfoxide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2S5	Abcam HEK293T ARL6IP1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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