Pelger-Huet anomaly

Summary

Pelger-Huet anomaly (MONDO:0008214) is a disease caused by LBR (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LBR (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 24

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Pelger-Huet anomaly
Mondo ID	MONDO:0008214
EFO	EFO:1001093
MeSH	D010381
OMIM	169400
DOID	DOID:9631
ICD-11	1210390183
NCIT	C85002
SNOMED CT	85559002
UMLS	C0030779
MedGen	10617
GARD	0009148
MedDRA	10029377
Is cancer (heuristic)	no

Also known as: ovoid neutrophil nuclei, developmental delay, epilepsy and skeletal abnormalities · Pelger Huet anomaly · Pelger-Huet anomaly · Pelger-Huet nuclear anomaly · PHA

Data availability: 24 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Pelger-Huet anomaly

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid 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

ClinVar germline variants

24 retrieved; paginated sample, class counts are floors:

6 pathogenic, 6 uncertain significance, 4 conflicting classifications of pathogenicity, 3 benign, 2 pathogenic/likely pathogenic, 1 likely benign, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
100900	NM_002296.4(LBR):c.1639A>G (p.Asn547Asp)	LBR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100902	NM_002296.4(LBR):c.32_35del (p.Val11fs)	LBR	Pathogenic	no assertion criteria provided
545626	NM_002296.4(LBR):c.1757G>A (p.Arg586His)	LBR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9527	NM_002296.4(LBR):c.1565-10_1565-5del	LBR	Pathogenic	no assertion criteria provided
9528	NM_002296.4(LBR):c.166-2A>G	LBR	Pathogenic	no assertion criteria provided
9529	NM_002296.4(LBR):c.1599_1605delinsCTAGAAG (p.Leu534_Leu535delinsTer)	LBR	Pathogenic	no assertion criteria provided
9531	NM_002296.4(LBR):c.1484-9A>G	LBR	Pathogenic	no assertion criteria provided
9532	NM_002296.4(LBR):c.1706C>G (p.Pro569Arg)	LBR	Pathogenic	no assertion criteria provided
1676661	NM_002296.4(LBR):c.235C>T (p.Arg79Ter)	LBR	Likely pathogenic	criteria provided, single submitter
369680	NM_002296.4(LBR):c.1747C>T (p.Arg583Ter)	LBR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
426800	NM_002296.4(LBR):c.1366C>G (p.Leu456Val)	LBR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
748574	NM_002296.4(LBR):c.271C>T (p.Pro91Ser)	LBR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
9530	NM_002296.4(LBR):c.356C>T (p.Pro119Leu)	LBR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1414465	NM_002296.4(LBR):c.860T>C (p.Ile287Thr)	LBR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1433684	NM_002296.4(LBR):c.261_262inv (p.Gly88Ser)	LBR	Uncertain significance	criteria provided, single submitter
2902022	NM_002296.4(LBR):c.505C>T (p.Arg169Cys)	LBR	Uncertain significance	criteria provided, multiple submitters, no conflicts
3672644	NM_002296.4(LBR):c.1097A>G (p.Tyr366Cys)	LBR	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891566	NM_002296.4(LBR):c.1486T>G (p.Cys496Gly)	LBR	Uncertain significance	criteria provided, single submitter
930347	NM_002296.4(LBR):c.166-12C>T	LBR	Uncertain significance	criteria provided, single submitter
1620500	NM_002296.4(LBR):c.1315-13T>C	LBR	Likely benign	criteria provided, multiple submitters, no conflicts
258616	NM_002296.4(LBR):c.117G>A (p.Val39=)	LBR	Benign	criteria provided, multiple submitters, no conflicts
258617	NM_002296.4(LBR):c.261T>C (p.Pro87=)	LBR	Benign	criteria provided, multiple submitters, no conflicts
258619	NM_002296.4(LBR):c.461G>A (p.Ser154Asn)	LBR	Benign	criteria provided, multiple submitters, no conflicts
295940	NM_002296.4(LBR):c.843A>G (p.Val281=)	LBR	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · 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
LBR	Strong	Autosomal dominant	Pelger-Huet anomaly	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LBR	Orphanet:1426	Greenberg dysplasia
LBR	Orphanet:448267	Regressive spondylometaphyseal dysplasia
LBR	Orphanet:779	Reynolds syndrome

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
LBR	HGNC:6518	ENSG00000143815	Q14739	Delta(14)-sterol reductase LBR	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LBR	Delta(14)-sterol reductase LBR	Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis.

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)
LBR	Enzyme (other)	yes	1.3.1.70	ERG24_DHCR-like, Tudor, Sterol_reductase_CS

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
bone marrow	1
thymus	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LBR	294	ubiquitous	marker	trabecular bone tissue, bone marrow, thymus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LBR	2,789

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LBR	Q14739	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. 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
Cholesterol biosynthesis	1	1142.0×	0.013	LBR
Cholesterol biosynthesis via desmosterol (Bloch pathway)	1	1142.0×	0.013	LBR
Initiation of Nuclear Envelope (NE) Reformation	1	601.0×	0.016	LBR
Regulation of MECP2 expression and activity	1	368.4×	0.017	LBR
Transcriptional Regulation by MECP2	1	317.2×	0.017	LBR
Nuclear Envelope (NE) Reassembly	1	292.8×	0.017	LBR
RHOD GTPase cycle	1	203.9×	0.020	LBR
RHOG GTPase cycle	1	148.3×	0.020	LBR
RHOC GTPase cycle	1	146.4×	0.020	LBR
Metabolism of steroids	1	137.6×	0.020	LBR
RAC2 GTPase cycle	1	126.9×	0.020	LBR
RAC3 GTPase cycle	1	119.0×	0.020	LBR
Mitotic Metaphase and Anaphase	1	96.8×	0.021	LBR
Mitotic Anaphase	1	96.8×	0.021	LBR
RHOA GTPase cycle	1	74.6×	0.025	LBR
CDC42 GTPase cycle	1	72.3×	0.025	LBR
M Phase	1	66.0×	0.025	LBR
RAC1 GTPase cycle	1	61.1×	0.025	LBR
RHO GTPase cycle	1	60.1×	0.025	LBR
Cell Cycle, Mitotic	1	48.2×	0.030	LBR
Cell Cycle	1	36.0×	0.038	LBR
Signaling by Rho GTPases	1	34.2×	0.038	LBR
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.038	LBR
Metabolism of lipids	1	31.6×	0.038	LBR
RNA Polymerase II Transcription	1	22.5×	0.051	LBR
Gene expression (Transcription)	1	17.8×	0.063	LBR
Generic Transcription Pathway	1	15.1×	0.071	LBR
Metabolism	1	11.6×	0.089	LBR
Signal Transduction	1	10.2×	0.098	LBR

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
neutrophil differentiation	1	1872.4×	0.002	LBR
random inactivation of X chromosome	1	936.2×	0.002	LBR
cholesterol biosynthetic process	1	421.3×	0.002	LBR

Therapeutics

Drug target analysis

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

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
LBR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
LBR	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LBR	1.3.1.70	DELTA14-sterol reductase

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	1	LBR
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
LBR	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.