HPDL

Summary

HPDL (4-hydroxyphenylpyruvate dioxygenase like, HGNC:28242) is a protein-coding gene on chromosome 1p34.1, encoding 4-hydroxyphenylpyruvate dioxygenase-like protein (Q96IR7). Iron-dependent dioxygenase that catalyzes the conversion of 4-hydroxyphenylpyruvate (4-HPPA) to 4-hydroxymandelate (4-HMA) in the mitochondria, one of the steps in the biosynthesis of coenzyme Q10 from tyrosine.

The protein encoded by this intronless gene localizes to mitochondria, where it may function as 4-hydroxyphenylpyruvate dioxygenase. Clinical studies have identified several bi-allelic variants in this gene that lower the level of the encoded protein and lead to a clinically variable form of pediatric-onset spastic movement disorder.

Source: NCBI Gene 84842 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 126 total — 16 pathogenic, 29 likely-pathogenic
• Phenotypes (HPO): 50
• MANE Select transcript: NM_032756

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28242
Approved symbol	HPDL
Name	4-hydroxyphenylpyruvate dioxygenase like
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC15668, 4-HPPD-L
Ensembl gene	ENSG00000186603
Ensembl biotype	protein_coding
OMIM	618994
Entrez	84842

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000334815

RefSeq mRNA: 1 — MANE Select: NM_032756 NM_032756

CCDS: CCDS519

Canonical transcript exons

ENST00000334815 — 1 exons

Exon	Start	End
ENSE00001339073	45326895	45328710

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 83.60.

FANTOM5 (CAGE): breadth broad, TPM avg 5.6236 / max 129.3559, expressed in 907 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2677	3.7297	674
2675	0.9868	521
2676	0.5270	323
2678	0.3801	179

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.60	gold quality
mucosa of transverse colon	UBERON:0004991	73.73	gold quality
ileal mucosa	UBERON:0000331	72.49	gold quality
tibialis anterior	UBERON:0001385	68.79	silver quality
hindlimb stylopod muscle	UBERON:0004252	68.70	gold quality
cerebellar cortex	UBERON:0002129	67.96	gold quality
cerebellar hemisphere	UBERON:0002245	67.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	67.88	gold quality
rectum	UBERON:0001052	67.25	gold quality
transverse colon	UBERON:0001157	66.74	gold quality
cerebellum	UBERON:0002037	66.24	gold quality
bone marrow cell	CL:0002092	65.93	silver quality
ventricular zone	UBERON:0003053	65.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	64.81	gold quality
esophagus mucosa	UBERON:0002469	63.31	gold quality
vermiform appendix	UBERON:0001154	63.03	gold quality
stromal cell of endometrium	CL:0002255	62.63	gold quality
body of stomach	UBERON:0001161	62.36	gold quality
prefrontal cortex	UBERON:0000451	62.13	gold quality
small intestine Peyer’s patch	UBERON:0003454	61.51	gold quality
muscle of leg	UBERON:0001383	61.45	gold quality
ganglionic eminence	UBERON:0004023	61.32	gold quality
tibial nerve	UBERON:0001323	61.17	gold quality
gastrocnemius	UBERON:0001388	61.12	gold quality
ectocervix	UBERON:0012249	61.06	gold quality
parotid gland	UBERON:0001831	60.90	gold quality
caudate nucleus	UBERON:0001873	60.49	gold quality
small intestine	UBERON:0002108	60.29	gold quality
mucosa of sigmoid colon	UBERON:0004993	59.73	silver quality
stomach	UBERON:0000945	59.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting HPDL, 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-548E-5P	99.89	72.73	4486
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-384	98.71	67.34	1229
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-1224-3P	97.24	65.92	851
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-664B-5P	96.74	67.50	509
HSA-MIR-151A-3P	95.52	65.29	516

Literature-anchored findings (GeneRIF, showing 5)

• Biallelic variants in HPDL, encoding 4-hydroxyphenylpyruvate dioxygenase-like protein, lead to an infantile neurodegenerative condition. (PMID:33188300)
• Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia. (PMID:33970200)
• Novel bi-allelic HPDL variants cause hereditary spastic paraplegia in a Chinese patient. (PMID:34515336)
• HPDL mutations identified by exome sequencing are associated with infant neurodevelopmental disorders. (PMID:35985664)
• A novel homozygous HPDL variant in Japanese siblings with autosomal recessive hereditary spastic paraplegia: case report and literature review. (PMID:38286980)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hpdl	ENSDARG00000101010
		ENSDARG00000113721
mus_musculus	Hpdl	ENSMUSG00000043155
rattus_norvegicus	Hpdl	ENSRNOG00000018143
caenorhabditis_elegans		WBGENE00016294

Paralogs (1): HPD (ENSG00000158104)

Protein

Protein identifiers

4-hydroxyphenylpyruvate dioxygenase-like protein — Q96IR7 (reviewed: Q96IR7)

Alternative names: Glyoxalase domain-containing protein 1

All UniProt accessions (1): Q96IR7

UniProt curated annotations — full annotation on UniProt →

Function. Iron-dependent dioxygenase that catalyzes the conversion of 4-hydroxyphenylpyruvate (4-HPPA) to 4-hydroxymandelate (4-HMA) in the mitochondria, one of the steps in the biosynthesis of coenzyme Q10 from tyrosine.

Subcellular location. Mitochondrion.

Disease relevance. Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA) [MIM:619026] An autosomal recessive neurodevelopmental disorder characterized by developmental delay manifesting in infancy, inability to walk independently, mild to severe intellectual disability, poor overall growth, progressive microcephaly, and axial hypotonia. Additional variable features include brainstem and cerebellar involvement, seizures, joint contractures, ocular disturbances, episodic respiratory failure, and facial dysmorphism. The disease may be caused by variants affecting the gene represented in this entry. Spastic paraplegia 83, autosomal recessive (SPG83) [MIM:619027] 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. SPG83 is characterized by juvenile onset of progressive lower limb spasticity resulting in gait instability. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 Fe cation per subunit.

Similarity. Belongs to the 4HPPD family.

RefSeq proteins (1): NP_116145* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005956	4OHPhenylPyrv_dOase	Family
IPR029068	Glyas_Bleomycin-R_OHBP_Dase	Homologous_superfamily
IPR037523	VOC_core	Domain
IPR041735	4OHPhenylPyrv_dOase_C	Domain
IPR041736	4OHPhenylPyrv_dOase_N	Domain

Catalyzed reactions (Rhea), 1 shown:

• 3-(4-hydroxyphenyl)pyruvate + O2 = (S)-4-hydroxymandelate + CO2 (RHEA:21376)

UniProt features (21 total): sequence variant 14, binding site 3, domain 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96IR7-F1	91.45	0.76

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 (3): 163; 258; 339

Mutagenesis-validated functional residues (1):

Position	Phenotype
258	loss of 4-hppa dioxygenase activity. impaired cell 3d growth.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2142789	Ubiquinol biosynthesis

MSigDB gene sets: 168 (showing top): GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS, chr1p34, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, NAKAMURA_METASTASIS, GOCC_MITOCHONDRIAL_MATRIX, REACTOME_METABOLISM_OF_VITAMINS_AND_COFACTORS, GOMF_DIOXYGENASE_ACTIVITY, NAKAMURA_METASTASIS_MODEL_UP, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_SINGLE_DONORS_WITH_INCORPORATION_OF_MOLECULAR_OXYGEN, HATADA_METHYLATED_IN_LUNG_CANCER_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, MARTENS_TRETINOIN_RESPONSE_DN, BHAT_ESR1_TARGETS_NOT_VIA_AKT1_UP

GO Biological Process (1): aromatic amino acid metabolic process (GO:0009072)

GO Molecular Function (6): 4-hydroxyphenylpyruvate dioxygenase activity (GO:0003868), metal ion binding (GO:0046872), 4-hydroxymandelate synthase activity (GO:0050585), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on single donors with incorporation of molecular oxygen (GO:0016701), dioxygenase activity (GO:0051213)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	2
oxidoreductase activity	2
amino acid metabolic process	1
carboxylic acid metabolic process	1
cation binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1126 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HPDL	GLOD5	A6NK44	582
HPDL	HGD	Q93099	518
HPDL	GLOD4	Q9HC38	448
HPDL	DYNLT4	Q5JR98	446
HPDL	FAM124B	Q9H5Z6	407
HPDL	MCEE	Q96PE7	405
HPDL	EXOC3L4	Q17RC7	395
HPDL	C9orf78	Q9NZ63	392
HPDL	AMDHD1	Q96NU7	358
HPDL	A0A2R8Y455	A0A2R8Y455	353
HPDL	FAH	P16930	353
HPDL	GSTZ1	O43708	350
HPDL	ALDH18A1	P54886	350
HPDL	IL2RG	P31785	349
HPDL	COMMD7	Q86VX2	348
HPDL	TAT	P17735	348

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MOSPD2	FLNA	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): HPDL (Reconstituted Complex), HPDL (Affinity Capture-RNA), HPDL (Cross-Linking-MS (XL-MS)), HPDL (Cross-Linking-MS (XL-MS)), HPDL (Affinity Capture-MS), M6PR (Co-fractionation), STMN1 (Co-fractionation), SUCLA2 (Co-fractionation), TMEM177 (Co-fractionation), TACO1 (Co-fractionation), TCOF1 (Co-fractionation), LSM12 (Co-fractionation), HTRA2 (Co-fractionation), RIF1 (Co-fractionation), TST (Co-fractionation)

ESM2 similar proteins: A0A061IR73, A5YM72, A6QR56, A8MXQ7, D3KCC4, D3Z7H8, I3L5V6, O19179, O95382, P0C263, P0DPD7, P0DPE1, P10938, P11086, P14061, P51656, P51657, P51840, P52785, P54777, Q02846, Q0V8J4, Q13608, Q1WNP0, Q2VPK5, Q561R2, Q5XIH9, Q643R3, Q6NVG1, Q6PAT0, Q6SZW1, Q6ZPS2, Q7TMC8, Q8IYX4, Q8IZ83, Q8IZY2, Q8K248, Q8N0W3, Q8N2G8, Q96EY9

Diamond homologs: E9CWP5, O06695, O23920, O42764, O48604, O52791, P0CW94, P23996, P32754, P32755, P49429, P69053, P80064, P93836, Q02110, Q18347, Q1E803, Q22633, Q27203, Q4WHU1, Q4WPV8, Q53586, Q5BKL0, Q5EA20, Q5ZT84, Q60Y65, Q6CDR5, Q6TGZ5, Q76NV5, Q872T7, Q96IR7, Q96X22, Q9ARF9, Q9I576, Q9S2F4, Q5XIH9, Q8K248, Q9I6P6, Q557J8, Q55810

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	29
Uncertain significance	59
Likely benign	10
Benign	3

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1184996	NM_032756.4(HPDL):c.527T>C (p.Leu176Pro)	Pathogenic
1224493	NM_032756.4(HPDL):c.353dup (p.Tyr118Ter)	Pathogenic
1224495	NM_032756.4(HPDL):c.954dup (p.Gly319fs)	Pathogenic
1344861	NM_032756.4(HPDL):c.835C>T (p.Gln279Ter)	Pathogenic
1455311	NC_000001.10:g.(?45793451)(45798111_?)del	Pathogenic
2221909	NM_032756.4(HPDL):c.789del (p.Pro264fs)	Pathogenic
2302879	NM_032756.4(HPDL):c.163_164del (p.Leu55fs)	Pathogenic
2389616	NM_032756.4(HPDL):c.759dup (p.Pro254fs)	Pathogenic
3106792	NM_032756.4(HPDL):c.698_699insTGGGCCAGCATTGTCCCCACTCTTGTTCTGGCTGAGTC (p.Leu234fs)	Pathogenic
4686579	HPDL, MET1ILE (VCV001344855.6)	Pathogenic
4686580	HPDL, 1-BP DEL, 789G (VCV002221909.2)	Pathogenic
979207	NM_032756.4(HPDL):c.342_343insTGCC (p.Ala115fs)	Pathogenic
979208	NM_032756.4(HPDL):c.779G>A (p.Gly260Glu)	Pathogenic
979211	NM_032756.4(HPDL):c.537G>C (p.Trp179Cys)	Pathogenic
979212	NM_032756.4(HPDL):c.149G>A (p.Gly50Asp)	Pathogenic
986813	NM_032756.4(HPDL):c.753C>A (p.His251Gln)	Pathogenic
1224494	NM_032756.4(HPDL):c.232G>A (p.Ala78Thr)	Likely pathogenic
1321134	NM_032756.4(HPDL):c.529_530del (p.Leu177fs)	Likely pathogenic
1326909	NM_032756.4(HPDL):c.736C>T (p.Gln246Ter)	Likely pathogenic
1326910	NM_032756.4(HPDL):c.800dup (p.Glu268fs)	Likely pathogenic
1328237	NM_032756.4(HPDL):c.1013T>C (p.Leu338Pro)	Likely pathogenic
1344847	NM_032756.4(HPDL):c.418G>A (p.Gly140Arg)	Likely pathogenic
1344848	NM_032756.4(HPDL):c.518C>A (p.Ser173Tyr)	Likely pathogenic
1344849	NM_032756.4(HPDL):c.788C>G (p.Thr263Arg)	Likely pathogenic
1344852	NM_032756.4(HPDL):c.769_771delinsTC (p.Gln257fs)	Likely pathogenic
1344853	NM_032756.4(HPDL):c.27C>A (p.Cys9Ter)	Likely pathogenic
1344854	NM_032756.4(HPDL):c.493A>C (p.Thr165Pro)	Likely pathogenic
1344857	NM_032756.4(HPDL):c.523_529del (p.Thr175fs)	Likely pathogenic
1344858	NM_032756.4(HPDL):c.995del (p.Thr332fs)	Likely pathogenic
1344859	NM_032756.4(HPDL):c.650T>C (p.Leu217Pro)	Likely pathogenic

SpliceAI

49 predictions. Top by Δscore:

Variant	Effect	Δscore
1:45327841:T:A	acceptor_gain	0.9200
1:45327837:T:TA	acceptor_gain	0.9100
1:45327840:CTG:C	acceptor_gain	0.7800
1:45327838:G:A	acceptor_gain	0.7500
1:45327842:G:GC	acceptor_gain	0.6100
1:45328161:T:TA	acceptor_gain	0.4200
1:45327724:CCCAG:C	donor_loss	0.3900
1:45327725:CCAG:C	donor_loss	0.3900
1:45327726:CAG:C	donor_loss	0.3900
1:45327727:AGGTG:A	donor_loss	0.3900
1:45327728:GG:G	donor_loss	0.3900
1:45327729:G:GC	donor_loss	0.3900
1:45327730:T:A	donor_loss	0.3900
1:45327731:G:GT	donor_loss	0.3600
1:45328145:G:T	acceptor_gain	0.3600
1:45327734:G:T	donor_gain	0.3300
1:45328143:CTG:C	acceptor_gain	0.3200
1:45327733:G:GT	donor_gain	0.3100
1:45328023:G:GT	donor_gain	0.3000
1:45328115:C:T	acceptor_gain	0.3000
1:45328163:G:C	acceptor_gain	0.3000
1:45328161:TGGAG:T	acceptor_gain	0.2900
1:45328220:TGGCA:T	acceptor_gain	0.2900
1:45328221:GGCAG:G	acceptor_gain	0.2900
1:45327427:G:GT	donor_gain	0.2700
1:45328098:A:AG	donor_gain	0.2700
1:45328107:A:T	acceptor_gain	0.2700
1:45328162:G:A	acceptor_gain	0.2700
1:45327103:G:GG	donor_gain	0.2600
1:45327590:C:T	donor_gain	0.2600

AlphaMissense

2355 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:45327887:T:C	F247L	0.988
1:45327889:C:A	F247L	0.988
1:45327889:C:G	F247L	0.988
1:45328124:T:C	F326L	0.987
1:45328126:C:A	F326L	0.987
1:45328126:C:G	F326L	0.987
1:45328193:T:C	F349L	0.985
1:45328195:T:A	F349L	0.985
1:45328195:T:G	F349L	0.985
1:45327584:T:C	F146L	0.984
1:45327586:C:A	F146L	0.984
1:45327586:C:G	F146L	0.984
1:45327240:T:C	F31S	0.983
1:45327309:T:C	F54S	0.981
1:45328177:G:C	R343S	0.980
1:45328177:G:T	R343S	0.980
1:45328176:G:T	R343M	0.977
1:45327585:T:C	F146S	0.971
1:45328157:T:C	F337L	0.969
1:45328159:C:A	F337L	0.969
1:45328159:C:G	F337L	0.969
1:45327186:T:C	F13S	0.967
1:45327388:C:A	N80K	0.967
1:45327388:C:G	N80K	0.967
1:45328083:T:C	I312T	0.967
1:45328165:G:C	E339D	0.966
1:45328165:G:T	E339D	0.966
1:45328176:G:C	R343T	0.966
1:45327888:T:C	F247S	0.964
1:45327239:T:C	F31L	0.962

dbSNP variants (sampled 300 via entrez): RS1001879687 (1:45325483 C>T), RS1002059633 (1:45326744 C>G), RS1002128865 (1:45328387 T>A), RS1003909326 (1:45326790 C>A,T), RS1003958739 (1:45327032 C>A,G,T), RS1003961904 (1:45327074 A>G), RS1004892685 (1:45329091 T>C), RS1005305329 (1:45325818 G>A), RS1006307377 (1:45328793 C>T), RS1007806544 (1:45326255 G>A,C), RS1007938400 (1:45329186 G>A), RS1008169788 (1:45327464 C>T), RS1008257379 (1:45325478 A>T), RS1008553507 (1:45327845 T>C,G), RS1009156610 (1:45325121 C>A)

Disease associations

OMIM: gene MIM:618994 | disease phenotypes: MIM:603513, MIM:619026, MIM:619027, MIM:608456, MIM:108600

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities	Strong	Autosomal recessive
spastic paraplegia 83, autosomal recessive	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Leigh syndrome	Moderate	AR

Mondo (4): neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (MONDO:0033613), spastic paraplegia 83, autosomal recessive (MONDO:0033614), familial adenomatous polyposis 2 (MONDO:0012041), spastic ataxia (MONDO:0017845)

Orphanet (6): Inherited congenital spastic tetraplegia (Orphanet:210141), Infantile neurodegeneration-progressive spasticity-intellectual disability-white matter lesions syndrome (Orphanet:641353), Autosomal recessive spastic paraplegia type 83 (Orphanet:631076), Attenuated familial adenomatous polyposis (Orphanet:220460), MUTYH-related polyposis (Orphanet:247798), Spastic ataxia (Orphanet:316226)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000505	Visual impairment
HP:0000527	Long eyelashes
HP:0000544	External ophthalmoplegia
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001258	Spastic paraplegia
HP:0001270	Motor delay
HP:0001371	Flexion contracture
HP:0001510	Growth delay
HP:0001531	Failure to thrive in infancy
HP:0002015	Dysphagia
HP:0002066	Gait ataxia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002151	Increased circulating lactate concentration
HP:0002307	Drooling
HP:0002317	Unsteady gait
HP:0002376	Developmental regression
HP:0002395	Lower limb hyperreflexia
HP:0002490	Increased CSF lactate

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C567853	Cerebral Palsy, Spastic Quadriplegic, 1 (supp.)
C563924	Colorectal Adenomatous Polyposis, Autosomal Recessive (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects expression, decreases expression, increases expression	3
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Estradiol	increases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ferrous chloride	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	affects cotreatment, increases expression	1
Allergens	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Demecolcine	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Ethyl Methanesulfonate	decreases 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_B1TU	Abcam HeLa HPDL KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02198092	Not specified	COMPLETED	Preliminary Evaluation of Septin9 in Patients With Hereditary Colon Cancer Syndromes
NCT03847532	Not specified	UNKNOWN	MUTYH-associated Polyposis
NCT06163365	Not specified	UNKNOWN	Inherited Cancer Early Diagnosis (ICED) Study
NCT07461246	Not specified	ACTIVE_NOT_RECRUITING	Familial Adenomatous Poliposys Italian Network (Rete Italiana Poliposi Adenomatosa Familiare)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04297891	Not specified	UNKNOWN	Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias