ACD-related short telomere syndrome

Summary

ACD-related short telomere syndrome (MONDO:0100569) is a disease caused by ACD (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ACD (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ACD-related short telomere syndrome
Mondo ID	MONDO:0100569
GARD	0026285
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ACD-related telomere biology disorder › ACD-related short telomere syndrome

Related subtypes (1): ACD-related long telomere syndrome

Subtypes (2): dyskeratosis congenita, autosomal dominant 6, dyskeratosis congenita, autosomal recessive 7

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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1058605	NM_001082486.2(ACD):c.617A>C (p.His206Pro)	ACD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 3 · 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
ACD	Strong	Semidominant	ACD-related short telomere syndrome	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACD	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
ACD	Orphanet:397692	Hereditary isolated aplastic anemia
ACD	Orphanet:618	Familial melanoma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ACD	HGNC:25070	ENSG00000102977	Q96AP0	Adrenocortical dysplasia protein homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACD	Adrenocortical dysplasia protein homolog	Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACD	Other/Unknown	no		TPP1/Est3, ACD

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACD	282	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACD	1,044

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACD	Q96AP0	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Depurination	1	1631.4×	0.005	ACD
Depyrimidination	1	951.7×	0.005	ACD
Base-Excision Repair, AP Site Formation	1	878.5×	0.005	ACD
Telomere C-strand synthesis initiation	1	815.7×	0.005	ACD
Processive synthesis on the C-strand of the telomere	1	761.3×	0.005	ACD
Telomere C-strand (Lagging Strand) Synthesis	1	761.3×	0.005	ACD
Base Excision Repair	1	713.8×	0.005	ACD
Removal of the Flap Intermediate from the C-strand	1	634.4×	0.005	ACD
Extension of Telomeres	1	601.0×	0.005	ACD
Telomere Extension By Telomerase	1	456.8×	0.006	ACD
Polymerase switching on the C-strand of the telomere	1	423.0×	0.006	ACD
Telomere Maintenance	1	368.4×	0.006	ACD
Meiosis	1	285.5×	0.008	ACD
Packaging Of Telomere Ends	1	219.6×	0.008	ACD
Chromosome Maintenance	1	211.5×	0.008	ACD
Recognition and association of DNA glycosylase with site containing an affected purine	1	203.9×	0.008	ACD
Cleavage of the damaged purine	1	203.9×	0.008	ACD
Reproduction	1	190.3×	0.008	ACD
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	1	184.2×	0.008	ACD
Cleavage of the damaged pyrimidine	1	184.2×	0.008	ACD
Inhibition of DNA recombination at telomere	1	167.9×	0.008	ACD
DNA Damage/Telomere Stress Induced Senescence	1	163.1×	0.008	ACD
Meiotic synapsis	1	141.0×	0.008	ACD
Cellular Senescence	1	137.6×	0.008	ACD
DNA Repair	1	98.5×	0.011	ACD
Cellular responses to stress	1	36.8×	0.029	ACD
Cell Cycle	1	36.0×	0.029	ACD
Cellular responses to stimuli	1	31.5×	0.032	ACD

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
segmentation	1	8426.0×	0.001	ACD
regulation of establishment of protein localization to telomere	1	5617.3×	0.001	ACD
telomere assembly	1	4213.0×	0.001	ACD
protection from non-homologous end joining at telomere	1	2407.4×	0.001	ACD
establishment of protein localization to telomere	1	2106.5×	0.001	ACD
protein localization to chromosome, telomeric region	1	1532.0×	0.002	ACD
telomere capping	1	1296.3×	0.002	ACD
urogenital system development	1	991.3×	0.002	ACD
telomere maintenance via telomerase	1	732.7×	0.002	ACD
negative regulation of telomere maintenance via telomerase	1	732.7×	0.002	ACD
positive regulation of telomere maintenance	1	510.7×	0.003	ACD
embryonic limb morphogenesis	1	401.2×	0.003	ACD
telomere maintenance	1	267.5×	0.004	ACD
skeletal system development	1	125.8×	0.009	ACD
intracellular protein transport	1	64.8×	0.015	ACD

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ACD	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	ACD

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)
ACD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.