Spastic paraplegia 86, autosomal recessive

Summary

Spastic paraplegia 86, autosomal recessive (MONDO:0030673) is a disease caused by ABHD16A (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ABHD16A (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 13

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		17	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	spastic paraplegia 86, autosomal recessive
Mondo ID	MONDO:0030673
OMIM	619735
Orphanet	631085
DOID	DOID:0112342
UMLS	C5676910
MedGen	1801286
GARD	0025605
Is cancer (heuristic)	no

Also known as: autosomal recessive spastic paraplegia type 86 · spastic paraplegia 86, autosomal recessive · SPG86

Data availability: 13 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › complex hereditary spastic paraplegia › spastic paraplegia 86, autosomal recessive

Related subtypes (49): hereditary sensory and autonomic neuropathy with spastic paraplegia, hereditary spastic paraplegia 15, hereditary spastic paraplegia 23, spastic paraplegia-glaucoma-intellectual disability syndrome, Troyer syndrome, MASA syndrome, hereditary spastic paraplegia 11, hereditary spastic paraplegia 24, hereditary spastic paraplegia 25, hereditary spastic paraplegia 27, hereditary spastic paraplegia 26, spastic paraplegia, optic atropy, and neuropathy, hereditary spastic paraplegia 18, hereditary spastic paraplegia 32, spastic ataxia 2, hereditary spastic paraplegia 39, hereditary spastic paraplegia 45, hereditary spastic paraplegia 44, hereditary spastic paraplegia 46, hereditary spastic paraplegia 53, hereditary spastic paraplegia 49, hereditary spastic paraplegia 54, hereditary spastic paraplegia 55, hereditary spastic paraplegia 43, hereditary spastic paraplegia 57, hereditary spastic paraplegia 64, hereditary spastic paraplegia 61, hereditary spastic paraplegia 63, glutamate pyruvate transaminase 2 deficiency, hereditary spastic paraplegia 74, autosomal recessive complex spastic paraplegia type 9B, hereditary spastic paraplegia 75, spastic paraplegia-severe developmental delay-epilepsy syndrome, autosomal recessive spastic paraplegia type 76, autosomal recessive spastic paraplegia type 78, autosomal dominant complex spastic paraplegia, maternally-inherited spastic paraplegia, fatty acid hydroxylase-associated neurodegeneration, autosomal recessive spastic paraplegia type 59, autosomal recessive spastic paraplegia type 60, autosomal recessive spastic paraplegia type 66, autosomal recessive spastic paraplegia type 67, autosomal recessive spastic paraplegia type 68, autosomal recessive spastic paraplegia type 69, autosomal recessive spastic paraplegia type 70, spastic paraplegia 84, autosomal recessive, spastic paraplegia 85, autosomal recessive, kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome, autosomal recessive complex spastic paraplegia due to kennedy pathway dysfunction

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

13 retrieved; paginated sample, class counts are floors:

5 pathogenic, 5 uncertain significance, 2 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1162195	NM_021160.3(ABHD16A):c.1370G>A (p.Arg457Gln)	ABHD16A	Pathogenic	no assertion criteria provided
1162196	NM_021160.3(ABHD16A):c.340C>T (p.Arg114Ter)	ABHD16A	Pathogenic	no assertion criteria provided
1341326	NM_021160.3(ABHD16A):c.835C>T (p.Gln279Ter)	ABHD16A	Pathogenic	no assertion criteria provided
4292648	NM_021160.3(ABHD16A):c.1402C>T (p.Arg468Ter)	ABHD16A	Pathogenic	criteria provided, single submitter
4292694	NM_021160.3(ABHD16A):c.514C>T (p.Arg172Ter)	ABHD16A	Pathogenic	criteria provided, multiple submitters, no conflicts
3363138	NM_021160.3(ABHD16A):c.1307+1G>A	ABHD16A	Likely pathogenic	criteria provided, single submitter
4538540	NM_021184.4(C6orf47):c.*684_*748del	C6orf47	Likely pathogenic	criteria provided, single submitter
1199390	NM_021160.3(ABHD16A):c.1333C>T (p.Arg445Ter)	ABHD16A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1199388	NM_021160.3(ABHD16A):c.353G>A (p.Arg118His)	ABHD16A	Uncertain significance	criteria provided, single submitter
1199389	NM_021160.3(ABHD16A):c.1226T>G (p.Leu409Arg)	ABHD16A	Uncertain significance	criteria provided, single submitter
1199392	NM_021160.3(ABHD16A):c.362A>T (p.Asn121Ile)	ABHD16A	Uncertain significance	criteria provided, single submitter
2671941	NM_021160.3(ABHD16A):c.260A>G (p.Tyr87Cys)	ABHD16A	Uncertain significance	criteria provided, multiple submitters, no conflicts
4533377	NM_021160.3(ABHD16A):c.1448-1G>A	ABHD16A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ABHD16A	Strong	Autosomal recessive	spastic paraplegia 86, autosomal recessive	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABHD16A	Orphanet:631085	Autosomal recessive spastic paraplegia type 86

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ABHD16A	HGNC:13921	ENSG00000204427	O95870	Phosphatidylserine lipase ABHD16A	gencc,clinvar
C6orf47	HGNC:19076	ENSG00000204439	O95873	Uncharacterized protein C6orf47	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABHD16A	Phosphatidylserine lipase ABHD16A	Phosphatidylserine (PS) lipase that mediates the hydrolysis of phosphatidylserine to generate lysophosphatidylserine (LPS).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABHD16A	Other/Unknown	no		AB_hydrolase_1, AB_hydrolase_fold, ABHD16_N
C6orf47	Other/Unknown	no		DUF4661

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
pituitary gland	1
right hemisphere of cerebellum	1
apex of heart	1
granulocyte	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABHD16A	134	ubiquitous	marker	pituitary gland, adenohypophysis, right hemisphere of cerebellum
C6orf47	133	ubiquitous	yes	granulocyte, mucosa of transverse colon, apex of heart

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABHD16A	885
C6orf47	487

Intra-cohort edges

A	B	Sources
ABHD16A	C6orf47	string_interaction

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABHD16A	O95870	89.90
C6orf47	O95873	57.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
prostaglandin catabolic process	1	8426.0×	4e-04	ABHD16A
phosphatidylserine catabolic process	1	4213.0×	4e-04	ABHD16A
monoacylglycerol catabolic process	1	2407.4×	4e-04	ABHD16A

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ABHD16A	ORLISTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABHD16A	1	4
C6orf47	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ORLISTAT	4	ABHD16A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ABHD16A	13	Binding:13

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
ORLISTAT	4	ABHD16A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABHD16A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	C6orf47

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
C6orf47	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.