Pellagra

Summary

Pellagra (MONDO:0019975) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• Phenotypes (HPO): 43

Clinical features

Signs & symptoms

Clinical features (HPO)

43 HPO clinical features (Orphanet curated; top 43 by frequency):

HPO ID	Term	Frequency
HP:0100497	Vitamin B3 deficiency	Very frequent (80-99%)
HP:0000992	Cutaneous photosensitivity	Frequent (30-79%)
HP:0002013	Vomiting	Frequent (30-79%)
HP:0002015	Dysphagia	Frequent (30-79%)
HP:0002018	Nausea	Frequent (30-79%)
HP:0002024	Malabsorption	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0004326	Cachexia	Frequent (30-79%)
HP:0004395	Malnutrition	Frequent (30-79%)
HP:0004396	Poor appetite	Frequent (30-79%)
HP:0005263	Gastritis	Frequent (30-79%)
HP:0007400	Irregular hyperpigmentation	Frequent (30-79%)
HP:0008066	Abnormal blistering of the skin	Frequent (30-79%)
HP:0010280	Stomatitis	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0012531	Pain	Frequent (30-79%)
HP:0031258	Delirium	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:0100753	Schizophrenia	Frequent (30-79%)
HP:0100825	Cheilitis	Frequent (30-79%)
HP:0000158	Macroglossia	Frequent (30-79%)
HP:0000206	Glossitis	Frequent (30-79%)
HP:0000716	Depression	Frequent (30-79%)
HP:0000726	Dementia	Frequent (30-79%)
HP:0000738	Hallucinations	Frequent (30-79%)
HP:0000958	Dry skin	Frequent (30-79%)
HP:0000962	Hyperkeratosis	Frequent (30-79%)
HP:0000988	Skin rash	Frequent (30-79%)
HP:0000613	Photophobia	Occasional (5-29%)
HP:0000712	Emotional lability	Occasional (5-29%)
HP:0000739	Anxiety	Occasional (5-29%)
HP:0001324	Muscle weakness	Occasional (5-29%)
HP:0002014	Diarrhea	Occasional (5-29%)
HP:0002019	Constipation	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0003401	Paresthesia	Occasional (5-29%)
HP:0007141	Sensorimotor neuropathy	Occasional (5-29%)
HP:0025300	Malar rash	Occasional (5-29%)
HP:0031987	Diminished ability to concentrate	Occasional (5-29%)
HP:0032448	Achlorhydria	Occasional (5-29%)
HP:0033505	Livedo reticularis	Occasional (5-29%)
HP:0100653	Optic neuritis	Occasional (5-29%)
HP:0200037	Skin vesicle	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	pellagra
Mondo ID	MONDO:0019975
MeSH	D010383
Orphanet	97352
DOID	DOID:8457
ICD-11	1108993080
SNOMED CT	418279001
UMLS	C0030783
MedGen	45364
GARD	0010014
MedDRA	10029400
Is cancer (heuristic)	no

Also known as: pellagra

Data availability: 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › pellagra

Related subtypes (71): dermatitis, cutaneous mucinosis, skin neoplasm, pyoderma, chronic ulcer of skin, systemic sclerosis, sunburn, severe cutaneous adverse reaction, paronychia, Achenbach syndrome, erythema multiforme, erythematosquamous dermatosis, exanthem, facial dermatosis, hand dermatosis, keratosis, leg dermatosis, lichen disease, lipodystrophy, mongolian spot, reactive cutaneous fibrous lesion, rosacea, scalp dermatosis, sebaceous gland disorder, skin atrophy, skin sarcoidosis, sweat gland disorder, vesiculobullous skin disease, hyperglobulinemic purpura, ainhum, cheilitis glandularis, erythema palmare hereditarium, multiple benign circumferential skin creases on limbs, actinic prurigo, congenital lethal erythroderma, Parana hard-skin syndrome, Bazex-Dupre-Christol syndrome, nephrogenic systemic fibrosis, erosive pustular dermatosis of the scalp, pseudoxanthoma elasticum-like papillary dermal elastolysis, toxic dermatosis, oral erosive lichen, chronic actinic dermatitis, Jessner lymphocytic infiltration of the skin, acquired kinky hair syndrome, primary cutaneous plasmacytosis, cutaneous pseudolymphoma, corticosteroid-sensitive aseptic abscess syndrome, interstitial granulomatous dermatitis with arthritis, epidermal disease, skin pigmentation disorder, skin vascular disease, Wells syndrome, solar urticaria, hereditary epidermal appendage anomaly, keratosis pilaris, dermis disorder, aquagenic pruritus, Boudhina Yedes Khiari syndrome, non-neoplastic nevus, cutaneous sclerosis, pityriasis rotunda, hematohidrosis, skin disorder caused by infection, livedoid vasculopathy, prurigo nodularis, granuloma faciale, sclerema neonatorum, hereditary skin disorder, hand-foot syndrome, Nicolau syndrome

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
KMO	Limited	Autosomal recessive	pellagra	2

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
KMO	HGNC:6381	ENSG00000117009	O15229	Kynurenine 3-monooxygenase	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KMO	Kynurenine 3-monooxygenase	Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KMO	Enzyme (other)	yes	1.14.13.9	FAD-bd, Kynurenine_monooxygenase, FAD/NAD-bd_sf

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
liver	1
palpebral conjunctiva	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KMO	194	broad	marker	right lobe of liver, palpebral conjunctiva, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KMO	3,494

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KMO	O15229	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Tryptophan catabolism	1	761.3×	0.004	KMO
Metabolism of amino acids and derivatives	1	67.6×	0.022	KMO
Metabolism	1	11.6×	0.086	KMO

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
obsolete L-kynurenine metabolic process	1	16852.0×	5e-04	KMO
kynurenic acid biosynthetic process	1	8426.0×	5e-04	KMO
positive regulation of glutamate secretion, neurotransmission	1	8426.0×	5e-04	KMO
obsolete anthranilate metabolic process	1	5617.3×	5e-04	KMO
obsolete kynurenine metabolic process	1	4213.0×	6e-04	KMO
L-tryptophan catabolic process	1	2808.7×	7e-04	KMO
response to salt stress	1	1872.4×	7e-04	KMO
NAD+ metabolic process	1	1872.4×	7e-04	KMO
‘de novo’ NAD+ biosynthetic process from L-tryptophan	1	1872.4×	7e-04	KMO
quinolinate biosynthetic process	1	1532.0×	8e-04	KMO
cellular response to interleukin-1	1	280.9×	0.004	KMO
cellular response to lipopolysaccharide	1	98.0×	0.010	KMO

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KMO	1	1

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GSK-065	1	KMO

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KMO	41	Binding:38, ADMET:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KMO	1.14.13.9	kynurenine 3-monooxygenase

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

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)
GSK-065	1	KMO

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	1	KMO
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.