SPG21

Summary

SPG21 (SPG21 abhydrolase domain containing, maspardin, HGNC:20373) is a protein-coding gene on chromosome 15q22.31, encoding Maspardin (Q9NZD8). May play a role as a negative regulatory factor in CD4-dependent T-cell activation.

The protein encoded by this gene binds to the hydrophobic C-terminal amino acids of CD4 which are involved in repression of T cell activation. The interaction with CD4 is mediated by the noncatalytic alpha/beta hydrolase fold domain of this protein. It is thus proposed that this gene product modulates the stimulatory activity of CD4. Mutations in this gene are associated with autosomal recessive spastic paraplegia 21 (SPG21), also known as mast syndrome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51324 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mast syndrome (Strong, GenCC)
• Clinical variants (ClinVar): 205 total — 6 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 37
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_016630

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20373
Approved symbol	SPG21
Name	SPG21 abhydrolase domain containing, maspardin
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	ACP33, GL010, BM-019, MAST, ABHD21
Ensembl gene	ENSG00000090487
Ensembl biotype	protein_coding
OMIM	608181
Entrez	51324

Gene structure

Transcript identifiers

Ensembl transcripts: 62 — 58 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000204566, ENST00000416889, ENST00000433215, ENST00000557795, ENST00000558339, ENST00000558415, ENST00000558765, ENST00000558943, ENST00000559199, ENST00000559677, ENST00000560564, ENST00000560878, ENST00000561078, ENST00000561088, ENST00000854124, ENST00000854125, ENST00000854126, ENST00000854127, ENST00000854128, ENST00000854129, ENST00000854130, ENST00000854131, ENST00000854132, ENST00000854133, ENST00000854134, ENST00000854135, ENST00000854136, ENST00000854137, ENST00000854138, ENST00000854139, ENST00000854140, ENST00000854141, ENST00000854142, ENST00000854143, ENST00000854144, ENST00000854145, ENST00000854146, ENST00000854147, ENST00000854148, ENST00000854149, ENST00000854150, ENST00000854151, ENST00000854152, ENST00000854153, ENST00000854154, ENST00000854155, ENST00000854156, ENST00000854157, ENST00000937873, ENST00000937874, ENST00000937875, ENST00000937876, ENST00000937877, ENST00000937878, ENST00000968546, ENST00000968547, ENST00000968548, ENST00000968549, ENST00000968550, ENST00000968551, ENST00000968552, ENST00000968553

RefSeq mRNA: 3 — MANE Select: NM_016630 NM_001127889, NM_001127890, NM_016630

CCDS: CCDS10198, CCDS45279

Canonical transcript exons

ENST00000204566 — 9 exons

Exon	Start	End
ENSE00001861950	64989665	64989914
ENSE00001949631	64963022	64963736
ENSE00003500865	64965320	64965460
ENSE00003510914	64970114	64970222
ENSE00003580742	64976475	64976555
ENSE00003589065	64980864	64981025
ENSE00003676302	64969255	64969362
ENSE00003687886	64983507	64983593
ENSE00003784400	64974602	64974747

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.6482 / max 367.7272, expressed in 1828 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150513	34.5648	1823
150511	29.3317	1818
150509	1.3886	732
150514	1.1003	810
150512	0.7747	530
150510	0.3168	131
207566	0.1714	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	98.25	gold quality
monocyte	CL:0000576	98.12	gold quality
mononuclear cell	CL:0000842	98.01	gold quality
leukocyte	CL:0000738	97.95	gold quality
right uterine tube	UBERON:0001302	97.54	gold quality
stromal cell of endometrium	CL:0002255	97.40	gold quality
secondary oocyte	CL:0000655	97.30	gold quality
oocyte	CL:0000023	97.27	gold quality
endocervix	UBERON:0000458	96.81	gold quality
islet of Langerhans	UBERON:0000006	96.67	gold quality
pericardium	UBERON:0002407	96.54	gold quality
mucosa of stomach	UBERON:0001199	96.53	gold quality
palpebral conjunctiva	UBERON:0001812	96.48	gold quality
granulocyte	CL:0000094	96.44	gold quality
right adrenal gland cortex	UBERON:0035827	96.43	gold quality
gall bladder	UBERON:0002110	96.31	gold quality
renal medulla	UBERON:0000362	96.30	gold quality
cauda epididymis	UBERON:0004360	96.24	gold quality
blood	UBERON:0000178	96.21	gold quality
rectum	UBERON:0001052	96.19	gold quality
duodenum	UBERON:0002114	96.16	gold quality
seminal vesicle	UBERON:0000998	96.14	gold quality
nipple	UBERON:0002030	96.14	gold quality
right adrenal gland	UBERON:0001233	96.13	gold quality
caput epididymis	UBERON:0004358	96.12	gold quality
smooth muscle tissue	UBERON:0001135	96.09	gold quality
urethra	UBERON:0000057	96.01	gold quality
periodontal ligament	UBERON:0008266	95.99	gold quality
trachea	UBERON:0003126	95.96	gold quality
left lobe of thyroid gland	UBERON:0001120	95.91	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

Upstream regulators (CollecTRI, top): FOXN1, ZFPM1

miRNA regulators (miRDB)

43 targeting SPG21, 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-1252-5P	100.00	69.80	2774
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
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-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 4)

• frameshift results in the premature termination of the encoded product, which is designated “maspardin” (Mast syndrome, spastic paraplegia, autosomal recessive with dementia) (PMID:14564668)
• Data report that maspardin localizes prominently to cytoplasm as well as to membranes, possibly at trans-Golgi network/late endosomal compartments, and that maspardin interacts with the aldehyde dehydrogenase ALDH16A1. (PMID:19184135)
• HBV X gene enhanced SPG21 gene promoter activity, SPG21 mRNA expression and SPG21 protein production in HepG2 cells in a dose-dependent manner. (PMID:21205478)
• SPG21, a potential oncogene targeted by miR-128-3p, amplifies HBx-induced carcinogenesis and chemoresistance via activation of TRPM7-mediated JNK pathway in hepatocellular carcinoma. (PMID:38753154)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	spg21	ENSDARG00000007760
mus_musculus	Spg21	ENSMUSG00000032388
rattus_norvegicus	Spg21	ENSRNOG00000015019

Protein

Protein identifiers

Maspardin — Q9NZD8 (reviewed: Q9NZD8)

Alternative names: Acid cluster protein 33, Spastic paraplegia 21 autosomal recessive Mast syndrome protein, Spastic paraplegia 21 protein

All UniProt accessions (9): Q9NZD8, H0YKB0, H0YKM6, H0YLD7, H0YLT5, H0YLW1, H0YMB7, H0YML6, H3BRR0

UniProt curated annotations — full annotation on UniProt →

Function. May play a role as a negative regulatory factor in CD4-dependent T-cell activation.

Subunit / interactions. Interacts with CD4. Interacts with ALDH16A1.

Subcellular location. Cytoplasm. Cytosol. Membrane. Endosome membrane. Golgi apparatus. trans-Golgi network membrane.

Tissue specificity. Expressed in all tissues tested, including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Expressed in J.CaM1.6, HuT 78 and HeLa cell lines (at protein level).

Disease relevance. Spastic paraplegia 21, autosomal recessive (SPG21) [MIM:248900] 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. SPG21 is associated with dementia and other central nervous system abnormalities. Subtle childhood abnormalities may be present, but the main features develop in early adulthood. The disease is slowly progressive, and cerebellar and extrapyramidal signs are also found in patients with advanced disease. Patients have a thin corpus callosum and white-matter abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the AB hydrolase superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZD8-1	1	yes
Q9NZD8-2	2

RefSeq proteins (3): NP_001121361, NP_001121362, NP_057714* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR026151	Maspardin	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF00561

UniProt features (8 total): sequence conflict 3, chain 1, domain 1, modified residue 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZD8-F1	93.02	0.86

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 (1): 304

Mutagenesis-validated functional residues (1):

Position	Phenotype
109	abolishes interaction with cd4.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 252 (showing top): GOBP_BEHAVIOR, MODULE_151, GCANCTGNY_MYOD_Q6, GOBP_NEURON_MATURATION, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_GROWTH, GOBP_NEUROGENESIS, CAGCTG_AP4_Q5, GOBP_RESPONSE_TO_EPIDERMAL_GROWTH_FACTOR, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_ERBB_SIGNALING_PATHWAY, GOBP_CELL_MATURATION, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, GOCC_COATED_VESICLE

GO Biological Process (10): epidermal growth factor receptor signaling pathway (GO:0007173), locomotory behavior (GO:0007626), gene expression (GO:0010467), neuron maturation (GO:0042551), collateral sprouting (GO:0048668), antigen receptor-mediated signaling pathway (GO:0050851), neuromuscular process (GO:0050905), limb development (GO:0060173), response to epidermal growth factor (GO:0070849), cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (2): CD4 receptor binding (GO:0042609), protein binding (GO:0005515)

GO Cellular Component (7): Golgi apparatus (GO:0005794), cytosol (GO:0005829), endosome membrane (GO:0010008), trans-Golgi network transport vesicle (GO:0030140), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
endomembrane system	2
ERBB signaling pathway	1
behavior	1
macromolecule biosynthetic process	1
cell maturation	1
neuron development	1
axonogenesis	1
developmental cell growth	1
developmental growth involved in morphogenesis	1
immune response-activating cell surface receptor signaling pathway	1
nervous system process	1
appendage development	1
response to growth factor	1
signal transduction	1
signaling receptor binding	1
binding	1
intracellular membrane-bounded organelle	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
Golgi-associated vesicle	1
transport vesicle	1
clathrin-coated vesicle	1
intracellular anatomical structure	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

870 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPG21	ALDH16A1	Q8IZ83	951
SPG21	SPG11	Q96JI7	949
SPG21	SPG7	Q9UQ90	905
SPG21	SPART	Q8N0X7	876
SPG21	AP5Z1	O43299	864
SPG21	PNPLA6	Q8IY17	860
SPG21	GJC2	Q5T442	820
SPG21	NIPA1	Q7RTP0	766
SPG21	SEMA6D	Q8NFY4	715
SPG21	ZFYVE26	Q68DK2	694
SPG21	TECPR2	O15040	668
SPG21	SPAST	Q9UBP0	654
SPG21	NPTN	Q9Y639	635
SPG21	DDHD2	O94830	620
SPG21	FA2H	Q7L5A8	617

IntAct

646 interactions, top by confidence:

A	B	Type	Score
SPG21	ATPAF2	psi-mi:“MI:0915”(physical association)	0.890
ATPAF2	SPG21	psi-mi:“MI:0915”(physical association)	0.890
AKIRIN2	SPG21	psi-mi:“MI:0915”(physical association)	0.890
SPG21	PRPS1	psi-mi:“MI:0915”(physical association)	0.830
SPG21	TRAF2	psi-mi:“MI:0915”(physical association)	0.830
PRPS1	SPG21	psi-mi:“MI:0915”(physical association)	0.830
TRAF2	SPG21	psi-mi:“MI:0915”(physical association)	0.830
SPG21	CRYAA	psi-mi:“MI:0915”(physical association)	0.780
SPG21	S100B	psi-mi:“MI:0915”(physical association)	0.780
SPG21	SPRED2	psi-mi:“MI:0915”(physical association)	0.780
DTX2	SPG21	psi-mi:“MI:0915”(physical association)	0.780
SPG21	FAM114A1	psi-mi:“MI:0915”(physical association)	0.780
SPG21	CUTC	psi-mi:“MI:0915”(physical association)	0.780
SPG21	RABAC1	psi-mi:“MI:0915”(physical association)	0.780
CRYAA	SPG21	psi-mi:“MI:0915”(physical association)	0.780
S100B	SPG21	psi-mi:“MI:0915”(physical association)	0.780
SPRED2	SPG21	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (260): SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid), SPG21 (Two-hybrid)

ESM2 similar proteins: A0A8J1LLF7, A0A974H8H3, A0MQH0, A4FUF0, A4IIY1, A5PK27, P09851, P15209, P20936, P24786, P42694, P50876, P50904, Q03351, Q09LZ8, Q16288, Q16620, Q25BN1, Q49A26, Q4KLT0, Q4R5H6, Q4V8I4, Q5F415, Q5IFJ9, Q5IS37, Q5IS82, Q5R7T2, Q5R8I6, Q5RES2, Q5RFV4, Q5RKH0, Q5RKN4, Q5XIC4, Q6DFV5, Q6DH94, Q6NW85, Q6PC62, Q6TUI4, Q6VNS1, Q7Z419

Diamond homologs: Q47GC1, Q47HL4, Q4R5H6, Q5FVD6, Q5RES2, Q5XIC4, Q6PC62, Q8MJJ1, Q9CQC8, Q9NZD8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	5
Uncertain significance	76
Likely benign	56
Benign	25

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
127082	NM_016630.7(SPG21):c.322G>C (p.Ala108Pro)	Pathogenic
1326870	NM_016630.7(SPG21):c.487del (p.Lys162_Ile163insTer)	Pathogenic
2490	NM_016630.7(SPG21):c.601dup (p.Thr201fs)	Pathogenic
2500987	NM_016630.7(SPG21):c.118del (p.Arg40fs)	Pathogenic
2720153	NM_016630.7(SPG21):c.137_138del (p.Leu46fs)	Pathogenic
989200	NM_016630.7(SPG21):c.345_346del (p.Gln116fs)	Pathogenic
1325118	NM_016630.7(SPG21):c.153del (p.Val52fs)	Likely pathogenic
1344117	NM_016630.7(SPG21):c.613C>T (p.Gln205Ter)	Likely pathogenic
1805260	NM_016630.7(SPG21):c.226-1G>A	Likely pathogenic
3899846	Single allele	Likely pathogenic
837857	NM_016630.7(SPG21):c.452+2T>C	Likely pathogenic

SpliceAI

1470 predictions. Top by Δscore:

Variant	Effect	Δscore
15:64965315:CTTA:C	donor_loss	1.0000
15:64965317:TACC:T	donor_loss	1.0000
15:64965456:AACAC:A	acceptor_gain	1.0000
15:64965458:CAC:C	acceptor_gain	1.0000
15:64965460:CC:C	acceptor_loss	1.0000
15:64965460:CCTT:C	acceptor_gain	1.0000
15:64965462:T:G	acceptor_loss	1.0000
15:64969242:A:C	donor_gain	1.0000
15:64969253:A:AC	donor_gain	1.0000
15:64969253:ACAT:A	donor_gain	1.0000
15:64969254:C:CC	donor_gain	1.0000
15:64969254:CAT:C	donor_gain	1.0000
15:64969254:CATC:C	donor_gain	1.0000
15:64969256:T:TA	donor_gain	1.0000
15:64970112:AC:A	donor_gain	1.0000
15:64970113:CC:C	donor_gain	1.0000
15:64974596:TCTTA:T	donor_loss	1.0000
15:64974597:CTTA:C	donor_loss	1.0000
15:64974598:TTACC:T	donor_loss	1.0000
15:64974599:TACCT:T	donor_loss	1.0000
15:64974600:A:AT	donor_loss	1.0000
15:64974745:AACC:A	acceptor_loss	1.0000
15:64974746:ACC:A	acceptor_loss	1.0000
15:64974747:CCTAA:C	acceptor_loss	1.0000
15:64974748:C:CA	acceptor_loss	1.0000
15:64980858:ACTT:A	donor_loss	1.0000
15:64980859:CTT:C	donor_loss	1.0000
15:64980860:TTACA:T	donor_loss	1.0000
15:64980861:TA:T	donor_loss	1.0000
15:64980862:A:AC	donor_gain	1.0000

AlphaMissense

2043 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:64980995:A:G	W32R	1.000
15:64980995:A:T	W32R	1.000
15:64969298:A:T	V209E	0.999
15:64969325:A:G	L200P	0.999
15:64969334:G:T	A197D	0.999
15:64970184:A:T	V164D	0.999
15:64974662:A:G	L131P	0.999
15:64974666:A:G	S130P	0.999
15:64974671:A:T	V128D	0.999
15:64974719:C:T	G112D	0.999
15:64974722:C:T	G111E	0.999
15:64974723:C:G	G111R	0.999
15:64974723:C:T	G111R	0.999
15:64974734:C:T	G107D	0.999
15:64976500:A:G	L94P	0.999
15:64965360:G:C	P257R	0.998
15:64965360:G:T	P257Q	0.998
15:64965362:G:C	F256L	0.998
15:64965362:G:T	F256L	0.998
15:64965364:A:G	F256L	0.998
15:64965372:C:T	G253E	0.998
15:64965381:A:G	L250P	0.998
15:64965387:G:T	A248D	0.998
15:64970196:A:G	L160P	0.998
15:64970196:A:T	L160H	0.998
15:64974625:G:C	F143L	0.998
15:64974625:G:T	F143L	0.998
15:64974627:A:G	F143L	0.998
15:64974643:G:C	F137L	0.998
15:64974643:G:T	F137L	0.998

dbSNP variants (sampled 300 via entrez): RS1000071764 (15:64987108 G>T), RS1000223194 (15:64978212 C>A), RS1000252112 (15:64970478 A>C,G), RS1000284519 (15:64975866 C>A,T), RS1000513349 (15:64972292 C>T), RS1000528973 (15:64990052 A>C,G), RS1000729866 (15:64971393 G>T), RS1000948857 (15:64967547 C>T), RS1000958690 (15:64967323 A>G), RS1001109962 (15:64973527 C>A,T), RS1001340849 (15:64986122 T>G), RS1001533903 (15:64991448 C>T), RS1001545340 (15:64991187 A>G), RS1001607472 (15:64965127 TG>T), RS1001756976 (15:64962906 A>G)

Disease associations

OMIM: gene MIM:608181 | disease phenotypes: MIM:248900, MIM:303350, MIM:620158

GenCC curated gene-disease

Disease	Classification	Inheritance
mast syndrome	Strong	Autosomal recessive

Mondo (3): mast syndrome (MONDO:0009568), hereditary spastic paraplegia (MONDO:0019064), spinocerebellar ataxia 50 (MONDO:0859334)

Orphanet (2): Autosomal recessive spastic paraplegia type 21 (Orphanet:101001), Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000726	Dementia
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001317	Abnormal cerebellum morphology
HP:0001347	Hyperreflexia
HP:0002015	Dysphagia
HP:0002059	Cerebral atrophy
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002075	Dysdiadochokinesis
HP:0002079	Hypoplasia of the corpus callosum
HP:0002186	Apraxia
HP:0002305	Athetosis
HP:0002311	Incoordination
HP:0002313	Spastic paraparesis
HP:0002476	Primitive reflex
HP:0003134	Abnormality of peripheral nerve conduction
HP:0003487	Babinski sign
HP:0003677	Slowly progressive
HP:0006892	Frontotemporal cerebral atrophy
HP:0007256	Abnormal pyramidal sign
HP:0007340	Lower limb muscle weakness
HP:0009830	Peripheral neuropathy

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C565409	MAST Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Doxorubicin	increases expression	1
Fluoxetine	increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Thiram	decreases expression	1
Tretinoin	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TQ18	HAP1 SPG21 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
NCT05354622	Not specified	RECRUITING	Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
NCT05373082	Not specified	COMPLETED	Identification of Modifying Factors in Hereditary Spastic Paraplegia
NCT05411627	Not specified	WITHDRAWN	A Pilot Study of Shockwave Therapy in HSP
NCT05432999	Not specified	COMPLETED	Extracorporeal Shockwave Therapy for Spasticity in People With Spinal Cord Injury
NCT05613114	Not specified	COMPLETED	Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia
NCT05767268	Not specified	COMPLETED	Assessment of the Psychophysical State During Rehabilitation Treatment With Lokomat
NCT05848271	Not specified	RECRUITING	Natural History Study of Patients with HPDL Mutations
NCT06156813	Not specified	RECRUITING	Turkish Lower-Extremity Motor Activity Log (LE-MAL)
NCT06229626	Not specified	RECRUITING	Evaluation of an Intensive Training Program for Patients with Hereditary Spastic Paraparesis SPG4/Spast
NCT06260982	Not specified	UNKNOWN	Cognitive Disorders in Hereditary Spastic Paraplegia Type 4
NCT06553976	Not specified	RECRUITING	Spastic Paraplegia - Centers of Excellence Research Network
NCT06572046	Not specified	RECRUITING	STOP-HSP.Net: a Registry for Hereditary Spastic Paraplegia as an Integration Tool for Future Therapeutic Strategies
NCT06573866	Not specified	RECRUITING	Enhancement of Quality of Work And Life
NCT06680063	Not specified	COMPLETED	Correlation Between Clinical Assessment and Neurophysiological Assessment in Spinal Cord Injury